bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term On-Line Hemodiafiltration Reduces Predialysis Beta-2-Microglobulin Levels in Chronic Hemodialysis Patients
Authors: Lin Chun-Liang , Yang Chih-Wei , Chiang Chin-Chen , Chang Ching-Tung , Huang Chiu-Ching
Published: April 2003

Background: Hemodiafiltration (HDF) is effective in delaying the surgical need for carpal tunnel syndrome in chronic hemodialysis patients, however, predialysis β2-microglobulin levels were not reduced in most short-term studies. The aim of this study was to assess the effect of long-term and differing frequencies of on-line HDF on serum β2-microglobulin levels in comparison to high-flux hemodialysis (HD). Methods: One hundred and twelve patients in the Chang Gung Memorial Hospital Dialysis Unit were divided into three groups to receive different frequencies of on-line HDF alternating with high-flux HD. Group 1 was treated once with HDF and twice with high-flux HD per week (n = 21). Group 2 was treated twice with HDF and once with high-flux HD per week (n = 33). Group 3 was treated with HDF three times per week (n = 58). Analysis was performed to compare the serum β2-microglobulin levels in these groups and to high-flux HD. Results: After receiving HDF for a mean of 7.9 months, group 3 patients had a reduced predialysis β2-microglobulin level (22.2 ±5.3 vs. 34.8 ±6.3 mg/l, p < 0.001), postdialysis β2-microglobulin level (6.3 ± 2.0 vs. 13.8 ± 6.8 mg/l, p < 0.001) and an increased β2-microglobulin reduction rate (76.1 ± 5.6 vs. 61.1 ± 13.3%, p = 0.03) when compared to high-flux HD. A significant improvement in URR (p = 0.0004), Kt/V (p = 0.0002) and TAC urea levels (p = 0.006) but not nPCR (p = 0.122) was found after patients had been treated with on-line HDF. The β2-microglobulin reduction rate was positively correlated with the overall volume of the replacement solution per session (p < 0.0001). Patients in group 3 had lower predialysis β2-microglobulin levels than those in group 1 and group 2 (22.2 ± 5.3 vs. 25.2 ± 7.2 vs. 26.0 ± 4.2 mg/l, p = 0.02). Furthermore, an inverse correlation was found between the predialysis β2-microglobulin level and the duration of HDF, if patients were treated for more than 12 months (p = 0.031). Conclusion: On-line HDF has an increased dialysis efficiency compared to high-flux dialysis. Long-term HDF further reduced predialysis β2-microglobulin levels, thus, it may provide an improved modality for renal replacement therapy.
Identifying the Value of Computers in Dialysis
Authors: Sargent John A.
Published: April 2003

Dialysis providers use computers to automate complicated tasks, ease staff burden, and develop knowledge or understanding to improve operations and patient care. Some applications are successful, others are not. Success can be economically quantified. Business – billing and accounts receivable computerization – can yield over USD 5.00 for USD 1.00 invested. The clinical case is more complex and difficult to economically justify. Computerization of clinical information for charge capture is the simplest application (< USD 1.00/treatment) yielding the greatest benefit. Economic benefits for improving quality of care through electronic medical records are more problematic. Provider benefit of clinical computing is strictly the net income from more dialysis treatments. Greater complexity – e.g., total electronic records – means more expensive systems and increased staff effort. Many systems cost in the USD 5.00 + range which must be paid by increasing provider overhead. Dialysis providers must determine the point where computerization no longer decreases operational costs as computing cost increases. This is a classical optimization problem; its solution is crucial to the economic health of the dialysis enterprise.
The Next Step from High-Flux Dialysis: Application of Sorbent Technology
Authors: Winchester James F. , Ronco Claudio , Brady James A. , Cowgill Larry D. , Salsberg Jamie , Yousha Eric , Choquette Mike , Albright Robert , Clemmer Jonathan , Davankov Vadim , Tsyurupa Maria , Pavlova Ludmila , Pavlov Mikhail , Cohen Gerald , Hörl Walter , Gotch Frank , Levin Nathan W.
Published: April 2003

The current foci of renal replacement therapy with dialysis are middle molecular weight toxins, consisting of small proteins, polypeptides and products of glycosylation and lipoxygenation. Conventional high-flux dialysis is not efficient at removing these molecules, explaining the increased interest in using sorbents to supplement dialysis techniques. Prototype biocompatible sorbents have been developed and investigated for middle molecule removal; these have been shown, in man, to remove β2-microglobulin, angiogenin, leptin, cytokines and other molecules, without reducing platelets and leukocytes. Extensive clinical studies are underway to demonstrate the clinical utility and safety of adding routinely a sorbent hemoperfusion device to hemodialysis.
Nocturnal Hypoxemia: A Neglected Cardiovascular Risk Factor in End-Stage Renal Disease?
Authors: Zoccali Carmine , Mallamaci Francesca , Tripepi Giovanni
Published: April 2003

Its is well established that sleep apnea (SA) is a health problem of paramount importance because it disrupts sleep and quality of life and may induce serious neuroendocrine and cardiovascular complications. There is little doubt that chronic renal failure is an independent cause of SA. The hypothesis that SA may depend on the accumulation of endogenous opioids still remains to be tested.Cytokines, particularly TNF-α and IL-6 which are much elevated in end-stage renal disease (ESRD), may also be implicated in the pathogenesis of SA. Nocturnal hypoxemia is an independent predictor of cardiovascular events in ESRD and the prediction power of this parameter remains strong and substantially unmodified after statistical adjustment for established cardiovascular risk factors in the dialysis population. Left ventricular hypertrophy and dysautonomia appear to be most likely intermediate mechanisms mediating the adverse cardiovascular effects of SA in ESRD.
Detection of Vascular Access Stenosis by Measurement of Access Blood Flow from Ionic Dialysance
Authors: Mercadal Lucile , Challier Emmanuel , Cluzel Philippe , Hamani Abdelaziz , Boulechfar Hacène , Boukhalfa Zhora , Izzedine Hassane , Bassilios Nader , Barrou Benoît , Deray Gilbert , Petitclerc Thierry
Published: April 2003

Background/Aim: The measurement of the vascular access blood flow rate (Qa) in chronic hemodialyzed patients was proposed to predict access thrombosis. We have recently presented a new method based on the measurements of ionic dialysance at normal and reversed positions of the blood lines. We evaluate the reliability of the measurement of Qa by this method in detecting significant access stenoses. Methods: Twenty-five patients on chronic hemodialysis and having a vascular access cannulated with two needles were studied. The Qa was evaluated by the Diascan® ionic dialysance (Qa-id) method and by the ultrasound dilution technique (Qa-us; Transonic®) during the same dialysis session. The measurements were available for 23 patients. In addition, the patients had ultrasonography of their fistula followed by angiography, if a stenosis was detected. Results: Qa-id and Qa-us were not significantly different, showing a difference in Qa at 32 ± 469 ml/min. Qa-id was significantly different between patients with or without stenosis (508 ± 241 vs. 1,125 ± 652 ml/min, p < 0.05). Among patients with a Qa <500 ml/min by Qa-id, 5 had a stenosis detected by ultrasonography (sensitivity 83%), and 3 had no stenosis (false-positive rate 18%). Of these 3 patients, 2 had a thrombotic event at 1 and 3 months, suggesting that a more sensitive detection of stenosis for this range of Qa is needed and that a Qa <500 ml/min has a higher power to predict thromboses than a stenosis by ultrasonography. Conclusions: The measurement of the access flow rate by the Qa-id method has a clinical relevance to the detection of vascular access stenosis. An intervention program based on the Qa-id has to be evaluated.
Keeping the Circuit Open: Lessons from the Lab
Authors: Shulman Rob I. , Singer Mervyn , Rock Jo
Published: April 2003

Background: Hemofiltration circuits generally require anticoagulation to prevent the membrane from clotting. Understanding the mechanisms involved in premature clotting of the filtration circuit is useful to optimize anticoagulation and maintain filter patency. Aims: To discuss research performed at our institution which throws light on the causes of premature clotting of the hemofilter, and to highlight our approach to anticoagulation. Discussion: Premature clotting of the circuit is related to low baseline levels of antithrombin III (AT-III), heparin co-factor II and tissue factor pathway inhibitor. Clotting is preceded by a precipitous rise in thrombin-antithrombin complexes, suggesting thrombin generation. Our standard anticoagulant is unfractionated heparin, where the primary mode of action is potentiation of endogenous AT-III. However, AT-III levels are diminished in sepsis and other causes of systemic inflammation. To supplement or prevent consumption of AT-III we use fresh frozen plasma or aprotinin (as cheaper alternatives to AT-III) in situations where filter life span is limited and mechanical obstruction has been excluded. Anticoagulation can be managed in heparin-induced thrombocytopenic patients with danaparoid, prostaglandins and/or predilution.
A Review of Plasma Exchange in Sepsis
Authors: Reeves John H.
Published: April 2003

Background: Severe sepsis involves a generalised inflammatory response, mediated by a number of cellular and humoral factors. Modulation of this response holds the promise of improved survival. Plasma exchange has been suggested as an adjunctive therapy in grave infective illnesses such as meningococcaemia, because it might remove harmful bacterial products and excessive endogenous inflammatory mediators. Aims: The aim of this article is to outline plasma exchange as an adjunctive therapy in sepsis, with an emphasis on the available clinical and experimental evidence for its use. Methods: A literature review was performed using Medline including all English language references to exchange transfusion, plasma exchange, plasmapheresis, plasma filtration and sepsis. Relevant texts and conference proceedings booklets were also hand searched. Results: Uncontrolled human data from case reports of more than 40 patients treated with plasma exchange for severe sepsis suggest a survival rate of over 70%. Animal studies produced conflicting results depending on the species and the model of sepsis employed. The only controlled clinical trial was too small to make conclusions regarding mortality. Conclusions: Plasma exchange remains an intuitively attractive but unproven therapy in sepsis. More controlled clinical trials are needed.
Acute Renal Failure after Cardiothoracic Surgery: A Review of Three Years Experience
Authors: Lawman S.H.A. , Cohen S.L. , Batson S.D.
Published: April 2003

2,683 cardiothoracic operations were carried out over a 3-year period. Patients requiring haemofiltration after surgery had a much greater mortality than those not haemofiltered. Of the 1,177 cardiothoracic intensive care unit (ICU) patients, 91 required haemofiltration for acute renal failure (ARF; 7.7%). Of the 1,506 cardiothoracic high-dependency unit patients 13 were transferred to the renal unit for dialysis (0.86%). Mortality for cardiothoracic patients overall was 14.4% and for those who required haemofiltration 58.7%. 74 of these haemofiltered patients had normal renal function preoperatively; mortality 61%. 15 patients had pre-existing renal impairment; mortality 53.3%. 15 patients were on dialysis prior to surgery; mortality 60%. Age was not a predictor of requirement for renal replacement therapy or of mortality. Operation type was a risk factor for ARF: of patients having a coronary artery bypass graft (CABG) 2.4% were filtered (mortality 37.8%), of patients having valve replacements 14.2% were haemofiltered (mortality 60.9%), and of the patients having redo-CABGs or redo-valve replacements 12.3% required haemofiltration (mortality 100%).
P-Glycoprotein Expression in Mouse Brain Increases with Maturation
Authors: Tsai Catherine E. , Daood Monica J. , Lane Robert H. , Hansen Thor W.R. , Gruetzmacher Elisa M. , Watchko Jon F.
Published: April 2003

The mdr1a isoform of P-glycoprotein (Pgp) is an integral plasma membrane efflux pump expressed in adult brain capillary endothelial cells and astrocytes of the blood-brain barrier. We determined the developmental pattern of Pgp expression in brain tissue at embryonic day 16 (E16), day of life 0 (D0), day of life 7 (D7), day of life 21 (D21), and adults (Ad). The relative expression of Pgp mRNA and protein was indexed as a percent (mean ± SEM) of D0 levels. Pgp mRNA levels increased significantly (p < 0.01) with maturation (E16: 75 ± 8%; D21: 303 ± 37%, and Ad: 1,160 ± 120%). Similarly, Pgp protein expression was observed at E16 and increased significantly (p < 0.01) during development (E16: 52 ± 8%; D7: 187 ± 23%; D21: 440 ± 48%, and Ad: 441 ± 56%). This developmental pattern of enhanced blood-brain barrier Pgp expression with maturation was confirmed by immunohistochemistry. We conclude that (i) Pgp expression in mouse brain is limited during late embryogenesis and the newborn period; (ii) Pgp expression increases markedly with postnatal maturation, and (iii) by D21 brain Pgp protein expression approximates adult levels.
Differential Stress Coping in Wild and Domesticated Sea Trout
Authors: Lepage Olivier , Øverli Øyvind , Petersson Erik , Järvi Torbjörn , Winberg Svante
Published: April 2003

Offspring of wild and sea-ranched (domesticated) sea trout (Salmo trutta) originating from the same river, were reared under identical hatchery conditions from the time of fertilization. At one year of age individual fish were exposed to two standardized stressors; transfer to a novel environment, with or without a simultaneous predator exposure. Blood plasma concentrations of glucose and cortisol were analyzed along with brain levels of dopamine (DA), 3,4-hydroxyphenylacetic acid (DOPAC, a major DA metabolite), serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindoleacetic acid (5 HIAA, a major 5-HT metabolite). Transfer to a novel environment, alone as well as in combination with predator exposure, resulted in elevated plasma concentrations of glucose and cortisol. Moreover, exposure to these stressors resulted in elevated brain levels of 5-HT and 5-HIAA, as well as elevated brain 5-HIAA/5-HT and DOPAC/DA ratios. Wild trout displayed significantly higher post stress plasma glucose levels than domesticated fish. Similarly, following stress, brain 5-HIAA/5-HT and DOPAC/DA ratios were significantly higher in wild than in domesticated fish. These differences were not caused by differences in brain levels of 5-HIAA and DOPAC, but instead by differences in brain 5-HT and DA concentrations. These results suggest that domestication results in attenuated stress responses in trout, and that alterations in brain monoamine neurotransmission are part of this effect.
Modulatory Effects of the Nucleus of the Basal Optic Root on Rotundal Neurons in Pigeons
Authors: Wang Yuan , Gu Yong , Wang Shu-Rong
Published: April 2003

The present paper reports for the first time in birds the modulatory effects of the nucleus of the basal optic root (nBOR) on visual neurons in the nucleus rotundus in particular and those of the accessory optic system on the tectofugal pathway in general. Pharmacological blockade of the nBOR by lidocaine led to a decrease or increase in visual responsiveness of rotundal cells, suggesting excitatory or inhibitory actions of the nBOR on rotundal cells. These results were confirmed by changes in the excitability of rotundal cells following electrical stimulation of the nBOR. Response latency measurements implied that there might be at least two pathways from the nBOR to the nucleus rotundus, one being a direct excitatory pathway and the other an indirect inhibitory pathway possibly mediated by the subpretectal nucleus and the interstitio-pretecto-subpretectal nucleus, which have been thought to send inhibitory afferents to the nucleus rotundus. Taken together with previous neuroanatomical and immunocytochemical studies, it is suggested that modulatory interactions might exist between the nBOR and the nRt in particular and between the accessory optic system and the tectofugal pathway in general in birds.
Sun Shades and Eye Size in Birds
Authors: Martin Graham R. , Katzir Gadi
Published: April 2003

Visual field width above the head is significantly correlated (rs = 0.92, n = 11, p < 0.001) with eye size in a sample of terrestrial birds that differ in their phylogeny and ecology. These species can be divided into two groups. Smaller-eyed sun-observers (axial length <18 mm) have comprehensive or near comprehensive visual coverage of the celestial hemisphere and are thus unable to avoid viewing the sun. Larger-eyed sun-avoiders (axial length >18 mm) have restricted visual fields and various types of optical adnexa (enlarged brows, hair like feathers on the eye lids and around the eye) which can prevent solar illumination of the cornea. We suggest that these differences relate to visual rather than pathological problems and argue that the reduction of disability glare, produced by sunlight falling directly upon the eye, becomes increasingly significant as eye size increases. We propose that the reduced visual fields and optical adnexa of the larger-eyed birds are primarily concerned with the maintenance of high spatial resolution.
The Relationships of Brain Stem Systems to Their Targets in the Spinal Cord of the Eel, Anguilla anguilla
Authors: Bosch T.J. , Roberts B.L.
Published: April 2003

We have investigated the detail with which supraspinal neurons innervate different regions in the spinal cord. Horseradish peroxidase was applied at different levels of the cord: (1) to the cut surface; (2) injected iontophoretically into one side; or (3) into one of the motoneuron pools innervating different muscle compartments. In all cases, labeled neurons were found throughout the brain distributed over nuclear groups identified in previous fish studies. Some cells from all but one of the nuclei have axons that extend over the whole length of the cord and about 50% of all neurons project to post-anal levels. No topographical distribution relating somal position and target location was found. Sixty seven percent of the neurons send axons to the ipsilateral side of the cord, although most nuclear groups provide a bilateral projection. Nucleus ruber projects entirely contralaterally. The descending and magnocellular octavolateral nuclei, and the descending nucleus of the trigeminal nerve project entirely ipsilaterally. Neurons that project to the spinal motoneuron pools innervating the myotomal red- or white-muscle are distributed throughout the same brain stem nuclei, but the cell bodies of those neurons innervating white-muscle motoneurons are larger. Nineteen pairs of cells were found to be consistently identifiable and all project to all levels of the cord; they were only labeled from injections made into the white-muscle motoneuron pool.
Brainstem Acoustic Areas in the Marine Catfish, Arius felis
Authors: McCormick Catherine A.
Published: April 2003

The marine catfish Arius felis produces low frequency sounds for communication and obstacle detection. It was hypothesized that the utriculus of the inner ear might play an important role in these behaviors. In the current study, brainstem acoustic areas were studied to reveal possible neuroanatomical specializations in utricular processing areas. The first-order octaval nuclei in Arius were identical in number, anatomical characteristics, and organization of saccular, lagenar, and utricular inputs to previous reports of these features in Ictalurus, a closely related species of catfish that does not exhibit the specialized acoustic behaviors present in Arius. Similarly, injections of neural tracer in the acoustic midbrain (nucleus centralis) of Arius revealed afferent and retrograde pathways almost identical to those previously reported in Ictalurus. It is suggested that areas within the primary and higher-order octaval nuclei that utilize utricular input in acoustic processing are likely identical in Arius and Ictalurus. Two sets of higher-order connections in Arius differ from those in Ictalurus. First, Arius apparently lacks the direct input from the anterior octaval nucleus to nucleus centralis reported in Ictalurus. Second, in Arius nucleus centralis projects bilaterally to a strip of neurons positioned ventral to the ventral boundary of the torus semicircularis. This projection is apparently absent in Ictalurus and in the related species Carassius (goldfish), but has been previously reported in Porichthyes, a sound-producing species belonging to a different teleost taxon.
Distribution of Neuronal Melanocortins in the Spadefoot Toad Spea multiplicata and Effects of Stress
Authors: Venkatesan S. , Carr J.A.
Published: April 2003

We examined the effects of an acute stressor on regional alpha-melanocyte-stimulating hormone (αMSH) content in the New Mexican spadefoot toad, Spea multiplicata. We first used immunocytochemistry along with radioimmunoassay (RIA) to examine the distribution of pro-opiomelanocortin (POMC) neurons in the brain of Spea. Neurons immunoreactive for αMSH, β-endorphin, and corticotropin were observed in the preoptic nucleus and ventral infundibulum of the hypothalamus. Ascending immunoreactive fibers projected to the olfactory nucleus, nucleus accumbens, and striatum. Numerous immunoreactive fibers were also observed in the hypothalamus. The thalamus/hypothalamus (T/HT) contained the greatest concentrations of αMSH as determined by RIA followed by the preoptic area (PO). Levels in the telencephalon, brain stem, and optic tectum (OT) were 14–23 times lower than in the T/HT. Exposure to a brief stressor elevated αMSH levels in the PO and OT. We conclude that Spea possesses two distinct POMC neuronal cell groups, one located in the anterior preoptic area and one located in the ventral infundibulum. Ascending projections to the basal ganglia might play an indirect role in tectal regulation and the control of prey-catching behavior. Exposure to an acute stressor alters brain αMSH content in Spea, although there are regional and temporal differences in the response pattern compared to Bufo. These findings are consistent with the notion that neuronal melanocortins influence how frogs and toads gather information about their environment during stress.
Brain Mediation of Anolis Social Dominance Displays
Authors: Baxter Jr. Lewis R. , Ackermann Robert F. , Clark Edward C. , Baxter John E.G.
Published: April 2003

Ritualistic displays of aggressive intent are important social signals, often obviating physically dangerous engagement. To date, however, brain regions mediating such behaviors are not established. Here we used male Anolis carolinensis together with an in vivo 14C-2-deoxyglucose method to determine patterns of brain activation during elicitation of this animal’s dominance displays vs. other behaviors. By patching one eye regional brain activation in the hemisphere receiving display-evocative visual stimuli (‘seeing’ side) was compared to activity in the contralateral brain that did not see specific stimuli (‘patched’ side); this was quantitated as the ratio of seeing/patched activity for brain regions of interest. Lone males displaying dominantly to mirrors activated dorsolateral basal ganglia (BG) in the seeing, compared to the patched hemisphere; this was not seen in various non-displaying controls. Degree of dorsolateral BG activation also correlated with a measure of dominant display activity, but not with locomotion. In socially stable pairs, displaying dominants showed similar activation of dorsolateral BG, but deactivated ventromedial BG; non-dominant cagemates displaying submissively had the opposite pattern. When cohabiting peacefully without displaying, paired dominants’ and subordinates’ brain activity patterns were similar to each other. Thus, different BG subsystems seem involved in dominant vs. submissive display behaviors. Given similarities in both social displays and BG organization, homologous brain systems might have similar functions in members of other amniote classes, including primates.
The Retinal Ganglion Cell Layer and Visual Acuity of the Camel
Authors: Harman Alison , Dann Jody , Ahmat Alicia , Macuda Todd , Johnston Kevin , Timneyb Brian
Published: April 2003

We examined the retinal ganglion cell layer of the dromedary camel, Camelus dromedarius. We have estimated that there are 8 million neurons in the ganglion cell layer of this large retina (mean area of 2,300 mm–2). However, only approximately 1 million are considered to be ganglion cells. The ganglion cells are arranged as two areas of high cell density, one in the temporal and one in the nasal retina. Densities of ganglion cells between these two high density regions is much lower, often less than 100 per mm–2. In between these two high density regions, on the nasal side of the optic nerve head, is a unique and dense vertical streak of mostly non-ganglion cells; the function of this specialization is unknown. On the basis of ganglion cell density we estimate that the peak acuity in the dromedary camel is about 10 and 9.5 cycles per degree in the temporal and nasal high density regions respectively and falls to 2–3 cycles per degree in the central retina. Behavioral acuity was estimated for one bactrian camel and was found to be approximately 10 cyc deg–1. The camel has a retina with a mean thickness of 104 µm, less than the 143 µm thickness that has previously been thought to be necessary for a retinal vasculature. Nevertheless, there is an extensive vitreal vasculature that does not appear to spare any retinal region.
A Quantitative Ultrastructural Study of the Optic Nerve of the Chameleon
Authors: Bennis Mohamed , El Hassni Meriem , Rio Jean-Paul , Lecren Denis , Repérant Jacques , Ward Roger
Published: April 2003

The optic nerve of adult chameleons was investigated with an electron microscope. The total number of retinal ganglion cell axons, the proportion of myelinated axons, the frequency distributions of myelinated and unmyelinated axon diameters were estimated, together with the volume occupied by glial processes. These were distinguished from unmyelinated axons using an antibody directed against glial fibrillary acidic protein, in a post-embedding procedure. The total number of fibers was estimated to be 405,235 ± 60,000 axons. The proportion of myelinated fibers varied with position between the eyeball and the chiasma; being 22–27% close to the eyeball, rising to 42–47% halfway along the optic nerve and to 56–62% close to the chiasma. Myelinated and unmyelinated fiber diameter distributions were unimodal and positively skewed, with modes of 0.7 µm and 0.2 µm, respectively. There was a significant regional variation in the size of optic nerve axons. Large myelinated axons were observed in the dorsal and ventral periphery, whereas smaller myelinated fibers and a high proportion of unmyelinated fibers were found in the center of the nerve.
Physiology and Morphology of Intratelencephalically Projecting Corticostriatal-Type Neurons in Pigeons as Revealed by Intracellular Recording and Cell Filling
Authors: Reiner Anton , Stern E.A. , Wilson C.J.
Published: April 2003

Much of the Wulst and dorsal ventricular ridge (DVR) in birds, which together make up the part of the avian telencephalon functionally resembling mammalian cerebral cortex, projects to the striatum. Those connections arise from neurons projecting additionally to the brainstem as well as from neurons projecting only within the telencephalon. As part of an effort to further characterize corticostriatal-type projection neurons in birds, we recorded intracellularly from neurons of the outer DVR, identified neurons projecting to the striatum by antidromic stimulation from the ipsilateral rostromedial striatum or subsequently by their axonal projection, characterized these neurons physiologically and then filled them with biocytin. As neurons in the outer DVR only project within telencephalon, neurons within it projecting to the striatum are of the intratelencephalically projecting (IT) type. Our studies suggest that: (1) the membrane potentials of avian IT-type neurons fluctuate between two preferred subthreshold values, and action potentials occur only in the ‘up’ state, (2) avian IT-type neurons show a time-dependent inward rectification in response to hyperpolarization and regular firing in response to constant current injection, (3) the conduction velocity of avian IT-type neurons is slow (about 0.2 m/s), (4) avian IT-type neurons possess radially disposed densely spiny dendrites but no apical dendrite, (5) avian IT-type neurons have local and distant collateral projections within the DVR, and (6) individual avian IT-type neurons give rise to an extensive terminal field within the striatum. Aside from the shape of their dendritic tree, IT-type neurons in birds closely resemble IT-type corticostriatal neurons in mammals in these various aspects, although it is presently uncertain whether this neuron type has been inherited in common by birds and mammals from stem amniotes.
Comparative Pharmacological Properties among Calcium Channel Blockers: T-Channel versus L-Channel Blockade
Authors: Noll Georg , Lüscher Thomas F.
Published: April 2003

Calcium antagonists are potent vasodilators and are widely used in the treatment of hypertension and angina pectoris. The currently available compounds belong to three classes: (1) dihydropyridines (e.g. nifedipine, amlodipine and felodipine), (2) phenylalkylamines (e.g. verapamil) and (3) benzothiazepines (e.g. diltiazem). The three classes differ in their pharmacological profile and safety. For example, verapamil and diltiazem lower heart rate, while dihydropyridines increase it or leave it unchanged. With most of the latter compounds, a marked activation of the sympathetic nervous system has been noted. Most compounds exhibit negative inotropic effects, particularly the first-generation molecules, which is disadvantageous in patients with impaired left-ventricular function. The most common side effects of these drugs are flushing, headache and edema. With verapamil, constipation may represent a problem in certain patients. Hence, in spite of a large number of calcium antagonists available, there remains a need for new compounds with enhanced efficacy and improved tolerability. A new compound should lack any negative inotropism, avoid any increase in sympathetic outflow or heart rate and exhibit a high degree of vascular selectivity. Furthermore, a low incidence of side effects, particularly ankle edema and optimal pharmacokinetics allowing once-daily dosing would be desirable. Mibefradil is a new calcium antagonist with promising pharmacological and clinical properties. The compound has a high bioavailability, lacks negative inotropic effects at therapeutic concentrations, does not exhibit reflex tachycardia during vasodilation and actually slightly decreases heart rate. It is a potent direct vasodilator efficacious in hypertension and chronic angina pectoris, elicits endothelium-dependent relaxations and facilitates the effects of nitric oxide in vascular smooth muscle. The drug is a particularly efficacious vasodilator in intramyocardial coronary arteries which may be important for its anti-ischemic effects and the lack of steal in the coronary circulation. Furthermore, mibefradil has antiproliferative properties in human vascular smooth muscle cells in culture. As a unique property, mibefradil blocks T-type calcium channels and hence represents a new class of calcium channel blockers. In patients with hypertension, mibefradil has a high efficacy in controlling blood pressure. The drug does not cause constipation and has a low incidence of ankle edema. A large trial is under way to further delineate the properties of this new calcium antagonist in patients with heart failure.
Calcium Channel Blockers in Heart Failure
Authors: Elkayam Uri
Published: April 2003

A considerable effort has been made in the last 15 years to evaluate the safety and efficacy of calcium channel blockers (CCBs) in the treatment of patients with chronic congestive heart failure (CHF). Available studies have provided strong evidence for a potential detrimental effect of the first-generation calcium antagonists in patients with CHF, indicating the need for great caution when these drugs are used in patients with significant depression of left ventricular systolic function. A number of second-generation CCB have demonstrated a strong vasodilatory effect and favorable hemodynamic action but failed to show a similar improvement in exercise capacity, morbidity and mortality. Moreover, drugs such as nicardipine and nisoldipine have resulted in a detrimental effect in some patients and, therefore, cannot be considered safe when used in patients with moderate-to-severe heart failure. Available information from the V-HeFT III study demonstrate a lack of an unfavorable effect of felodipine on exercise tolerance in patients with chronic heart failure. Although mortality rate was similar in both the felodipine and the placebo group, because of the relatively small number of patients in this study, no clear conclusion can be drawn regarding the effect of felodipine on mortality in patients with CHF. An encouraging signal regarding a potential role of CCB in the treatment of chronic heart failure has been provided by the recently completed PRAISE study. This prospective large-scale study demonstrated the safety of amlodipine, a long-acting dihydropyridine derivative, when used in patients with heart failure due to coronary artery disease. Furthermore, this study demonstrated a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy and provided a strong indication for a potential therapeutic benefit of amlodipine when added to standard CHF therapy in this patient population. No clear explanation is available at the present time regarding the reason for the deleterious effect demonstrated with some of the dihydropyridines and the contrasting benefit seen with amlodipine. Finally, more information regarding the safety and efficacy of dihydropyridines should become available in the next year. The PRAISE II study is ongoing and will provide further information regarding the therapeutic role of amlodipine in patients with nonischemic dilated cardiomyopathy. The MACH-1 study is evaluating the effect of mibefradil, a predominant T-type channel blocker with an ideal activity profile, on morbidity and mortality in patients with chronic CHF.
Clinical Advantage of Valsartan
Authors: McInnes Gordon T.
Published: April 2003

Valsartan is a specific angiotensin II receptor antagonist with high selectivity for the AT1 receptor subtype. After oral administration of single or repeated once-daily doses, valsartan 40–80 mg inhibits the pressor response to angiotensin II for 24 hours. In patients with mild-to-moderate hypertension, efficacy of valsartan appears to be independent of age, sex, and race, and is at least equivalent to that of calcium antagonists, ACE inhibitors, or thiazide diuretics. Response rate to valsartan 160 mg o.d. is significantly greater than after receiving losartan 100 mg o.d. Valsartan has additive effects with other antihypertensive drugs and combination therapy is effective in severe hypertension and in hypertension with renal insufficiency, where renal function is well maintained. Valsartan has good tolerability with a side-effect profile indistinguishable from placebo and superior to that of comparable drugs. Valsartan does not cause cough or adverse metabolic effects; first dose hypotension and rebound hypertension on abrupt withdrawal have not been encountered. Valsartan has clear clinical advantage in the management of hypertension. Its impact on prognosis in patients with a high risk of cardiovascular morbidity and mortality is under evaluation.
Prevention of Heart Failure
Authors: Cohn J.N.
Published: April 2003

Heart failure (HF) is a progressive process and the objective of treatment should be to prevent progression. Treatment should begin at the stage of asymptomatic left ventricular dysfunction (LVD), not only to reduce mortality but also to preserve exercise capacity and quality of life. To prevent clinical progression in patients with asymptomatic LVD or HF, left ventricular remodelling and dilatation must be prevented. The SOLVD prevention trial – the only clinical trial on the prevention of HF – showed that ACE inhibition significantly reduced the development of HF, but did not significantly reduce mortality. Plasma norepinephrine is elevated in patients with asymptomatic LVD, is further elevated in patients with overt HF, and is correlated with increased mortality. Inhibition of the sympathetic nervous system by administration of β-blocking agents is therefore a logical treatment for patients with HF or asymptomatic LVD. Clinical trials have shown that β-blocking agents increase left ventricular ejection fraction and reduce left ventricular dimensions in patients with HF, indicating regression of left ventricular remodelling. Almost all the patients in these studies were receiving an ACE inhibitor as part of their background medication, therefore the relative efficacy of β-blocking agents and ACE inhibitors in the regression of remodelling is not known. CARMEN, a double-blind, randomised, parallel group study of carvedilol versus enalapril versus carvedilol + enalapril in 450 patients with mild HF, will provide this information.
Idiopathic Short QT Interval:A New Clinical Syndrome?
Authors: Gussak Ihor , Brugada Pedro , Brugada Josep , Wright R. Scott , Kopecky Stephen L. , Chaitman Bernard R. , Bjerregaard Preben
Published: April 2003

In this first clinical report of an idiopathic familial persistently short QT interval (QTI), we describe three members of one family (a 17-year-old female, her 21-year-old brother, and their 51-year-old mother) demonstrating this ECG phenomenon, associated in the 17-year-old with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion. Similar ECG changes seen in an unrelated 37-year-old patient were associated with sudden cardiac death. Our report also describes other manifestations of abnormal shortening of the QTI and considers the possible arrhythmogenic potential of the short QTI.
Rhabdomyolysis and Acute Renal Failure after Changing Statin-Fibrate Combinations
Authors: Oldemeyer J. Bradley , Lund Richard J. , Koch Matt , Meares A. John , Dunlay Robert
Published: April 2003

Statin-fibrate combinations are commonly used to treat hyperlipidemia. These drugs have been previously reported to cause rhabdomyolysis with acute renal failure. Whether different statin-fibrate combinations have different risks for rhabdomyolysis is not known. We report a patient who developed rhabdomyolysis with acute renal failure pomptly after switching from the combination of pravastatin and fenofibrate to simvastatin and gemfibrozil.
Effects of Chronic Nitrate Therapy on Left-Ventricular Volume in Patients with Heart Failure Secondary to Coronary Disease Already Treated with Captopril: A Withdrawal Study
Authors: Wieshammer Siegfried , Hetzel Martin , Hetzel Jürgen , Henze Eberhard , Hombach Vinzenz
Published: April 2003

Objective: This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics. Patients and Methods: The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period. Results: The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 ± 15 W, nitrate group 68 ± 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 ± 4.0%; nitrate withdrawal: –2.7 ± 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (–9 ± 35 vs. 23 ± 48 ml, p < 0.02) and end-systolic volume (–9 ± 33 vs. +24 ± 47 ml; p < 0.01). Conclusion: The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.
Clinical Benefit and Approach of Ultrafiltration in Acute Heart Failure
Authors: Sharma Amit , Hermann Denise D. , Mehta Ravindra L.
Published: April 2003

Because of the increasing incidence of acute heart failure admissions to critical care units, nephrologists have been asked to become more involved in the management of these patients. Renal dysfunction is a major element in impeding clinical recovery. In acute heart failure, renal function is often abnormal. The judicious application of ultrafiltration techniques may represent an efficacious adjunct to present conventional practice. In patients with refractory congestive heart failure, the ability to provide continuous, daily, large volume removal not only improves volume status but also the clinical symptoms of the decompensated patient. A thorough literature review supports the premise that starting hemofiltration is an appropriate alternative for difficult and unstable cardiac patients. An optimal strategy utilizing continuous renal replacement therapy can dramatically improve the patient’s clinical condition, mitigate the neurohumoral stimulation, increase urinary output and promote absorption of excessive extravascular fluid.
A New Guidewire Technique for Difficult Cardiac Catheterization
Authors: Liau Chiau-Suong , Ho Shinn-Ge , Chen Sung-Nan , Yang Li-Fen
Published: April 2003

Purpose: To propose a simple guidewire technique to resolve the problem of difficulty in advancing catheters or guidewires during vascular and cardiac catheterization. Methods: A 0.035-inch J-tip guidewire was reshaped manually at the distal 7- to 8-cm portion, including the flexible part and 2–3 cm of the stiff part, into zigzag shape. With this modification, the guidewire became much more trackable and could be advanced to the right position. Results: In the past 2 years, this ‘zigzag wire technique’ was applied in cardiac catheterization with high success rates for cases with difficulty in advancing either catheters or guidewires. This wire technique was applied in peripheral arterial tortuosity or stenosis (18 cases, with success in 17), aortic aneurysm (successful in all 7 cases), aortic stenosis (11 cases, successful in 8), and dilated right heart chambers (successful in all 6 cases). No complications resulted from the use of this guidewire technique. Conclusion: This simple method of guidewire modification would be very helpful in difficult vascular and cardiac catheterization when difficulty in advancing catheters or wires was encountered.
Fluoride Uptake in Human Teeth from Fluoride–Releasing Restorative Material in vivo and in vitro: Two–Dimensional Mapping by EPMA–WDX
Authors: Yamamoto H. , Iwami Y. , Unezaki T. , Tomii Y. , Ebisu S.
Published: April 2003

Class V cavities were prepared in the upper and lower left second premolars from an individual under infiltration anesthesia. The cavities were filled with fluoride– releasing resin (TF). One month later, the teeth were extracted. As a control (in vitro), the upper and lower right second premolars were extracted at the time of the cavity preparation in vivo. Immediately after extraction, class V cavities were prepared and filled with TF, and immersed in normal saline solution for 1 month at 37°C. All four premolars were bisected longitudinally and the fluoride uptake around the cavity wall on the cut surface was measured using an electron probe microanalyzer–wavelength dispersive X–ray method. The fluoride uptake was given in the form of a two–dimensional map. Comparison of the observed values of each corresponding part of the tooth in vivo and in vitro revealed no characteristic differences. The maps were quite analogous as a whole.
Effect of a Water Rinse on ‘Labile’ Fluoride and Other Ions in Plaque and Saliva before and after Conventional and Experimental Fluoride Rinses
Authors: Vogel G.L. , Zhang Z. , Chow L.C. , Schumacher G.E.
Published: April 2003

Labile reservoirs are important in maintaining ion concentrations in oral fluids, especially after a fluoride dentifrice application, where a persistent increase in fluid fluoride can mitigate or reverse caries progression. In this study, the effect of experimental and conventional fluoride rinses on the in vitro and in vivo water–induced release of fluoride, calcium, phosphate, acetate and hydrogen ions from oral reservoirs was examined. At the start of each experiment, 13 subjects rinsed either with a conventional 228–ppm fluoride NaF rinse, a 228–ppm fluoride controlled–release rinse (CR rinse) or received no rinse. Sixty minutes later upper and lower molar plaque samples and 1–min saliva samples were collected. The subjects then rinsed with deionized water for 1 min, and 7 min later, a second set of samples was collected (in vivo study). Plaque fluid and clarified saliva were then recovered from samples by centrifugation, and the remaining plaque mass was sequentially extracted with water and acid to measure the water–extracted and total whole–plaque fluoride (in vitro study). All the samples were analyzed using microtechniques for pH, free calcium, phosphate, organic acids (plaque fluid) and fluoride (plaque fluid, centrifuged saliva and plaque extracts). Results showed that in vivo water rinsing decreased acetate and phosphate in plaque fluid, and fluoride in plaque fluid and saliva, but had no effect on plaque fluid pH. In vivo water rinsing, however, increased plaque fluid free calcium, apparently due to water–induced loss of calcium–binding ions. Water– or fluoride–rinse–induced changes in plaque fluid concentration were greater at the lower molar site, suggesting that rinse pooling may influence ion distribution. Before the water rinse, plaque fluid, saliva and whole–plaque total fluoride values were 1.7, 2 and 4 times higher after the CR rinse compared to the NaF rinse. Furthermore, the CR rinse deposited approximately 11 times more water–extracted fluoride compared to the NaF rinse, suggesting a ‘more efficient’ precipitation of ‘labile’ or ‘loosely bound fluoride’. The results presented here, and in previous studies, suggest the possibility of formulating effective fluoride dentifrices with a lower fluoride content than is currently in use.