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Biomedical subjects

A Roth

Publications and source records attributed to A Roth.

At least 91 records · Page 5Linked to original sources

Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex.

1. Dual voltage recordings were made from pairs of adjacent, synaptically connected thick tufted layer 5 pyramidal neurones in brain slices of young rat (14-16 days) somatosensory cortex to examine the physiological properties of unitary EPSPs. Pre- and postsynaptic neurones were filled with biocytin and examined in the light and electron microscope to quantify the morphology of axonal and dendritic arbors and the number and location of synaptic contacts on the target neurone. 2. In 138 synaptic connections between pairs of pyramidal neurones 96 (70%) were unidirectional and 42 (30%) were bidirectional. The probability of finding a synaptic connection in dual recordings was 0.1. Unitary EPSPs evoked by a single presynaptic action potential (AP) had a mean peak amplitude ranging from 0.15 to 5.5 mV in different connections with a mean of 1.3 +/- 1.1 mV, a latency of 1.7 +/- 0.9 ms, a 20-80% rise time of 2.9 +/- 2.3 ms and a decay time constant of 40 +/- 18 ms at 32-24 degrees C and -60 +/- 2 mV membrane potential. 3. Peak amplitudes of unitary EPSPs fluctuated randomly from trial to trial. The coefficient of variation (c.v.) of the unitary EPSP amplitudes ranged from 0.13 to 2.8 in different synaptic connections (mean, 0.52; median, 0.41). The percentage of failures of single APs to evoke a unitary EPSP ranged from 0 to 73% (mean, 14%; median, 7%). Both c.v. and percentage of failures decreased with increasing mean EPSP amplitude. 4. Postsynaptic glutamate receptors which mediate unitary EPSPs at -60 mV were predominantly of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor type. Receptors of the N-methyl-D-aspartate (NMDA) type contributed only a small fraction (< 20%) to the voltage-time integral of the unitary EPSP at -60 mV, but their contribution increased at more positive membrane potentials. 5. Branching patterns of dendrites and axon collaterals of forty-five synaptically connected neurones, when examined in the light microscope, indicated that the axonal and dendritic anatomy of both projecting and target neurones and of uni- and bidirectionally connected neurones was uniform. 6. The number of potential synaptic contacts formed by a presynaptic neurone on a target neurone varied between four and eight (mean, 5.5 +/- 1.1 contacts; n = 19 connections). Synaptic contacts were preferentially located on basal dendrites (63%, 82 +/- 35 microns from the soma, n = 67) and apical oblique dendrites (27%, 145 +/- 59 microns, n = 29), and 35% of all contacts were located on tertiary basal dendritic branches. The mean geometric distances (from the soma) of the contacts of a connection varied between 80 and 585 microns (mean, 147 microns; median, 105 microns). The correlation between EPSP amplitude and the number of morphologically determined synaptic contacts or the mean geometric distances from the soma was only weak (correlation coefficients were 0.2 and 0.26, respectively). 7. Compartmental models constructed from camera lucida drawings of eight target neurones showed that synaptic contacts were located at mean electrotonic distances between 0.07 and 0.33 from the soma (mean, 0.13). Simulations of unitary EPSPs, assuming quantal conductance changes with fast rise time and short duration, indicated that amplitudes of quantal EPSPs at the soma were attenuated, on average, to < 10% of dendritic EPSPs and varied in amplitude up to 10-fold depending on the dendritic location of synaptic contacts. The inferred quantal peak conductance increase varied between 1.5 and 5.5 nS (mean, 3 nS). 8. The combined physiological and morphological measurements in conjunction with EPSP simulations indicated that the 20-fold range in efficacy of the synaptic connections between thick tufted pyramidal neurones, which have their synaptic contacts preferentially located on basal and apical oblique dendrites, was due to differences in transmitter release probability of the projecting neurones and, to a lesser extent, to differenc

Action Potentials↗

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase.

BACKGROUND: It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS: Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS: These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.

Adult↗

Usefulness of self-administration of intramuscular lidocaine in the prehospital setting for ventricular tachyarrhythmias unassociated with acute myocardial infarction (the "Shahal" experience in Israel).

We report on the experience accumulated by the subscribers of SHAHAL cardiac services who self-injected intramuscular lidocaine (using an automatic injector "LidoPen") for documented ventricular tachyarrhythmias which were not associated with an acute myocardial infarction. SHAHAL provides professional care to its subscribers who telephone a monitor center and describe their symptoms, whereupon therapeutic measures are decided upon. Patient data are stored in a central computer, and the center can dispatch mobile intensive care units. All subscribers carry a portable transtelephonic electrocardiographic transmitter and are provided with the LidoPen. Indications for self-injection were: transmission of a wide-QRS tachycardia (rate > 100 beats/min), symptomatic multiple or complex ventricular premature complexes in association with chest discomfort, and when the time of arrival of a medical team to the patient was estimated to be at least 8 to 10 minutes. Successful usage of the LidoPen was reported in 137 cases (123 patients). An additional 11 patients failed to use the injector properly. There was a success rate in abolishing rapid sustained ventricular tachycardia (27 of 76 patients) and nonsustained ventricular tachycardia and/or multiple and complex ventricular ectopic activity (8 of 30 patients) of 33% (total 35 of 106 patients). In another 9%, those arrhythmias were slowed markedly. The remaining 31 cases were eventually interpreted as being of supraventricular origin. No complications attributed to the use of the injector were reported and its use was found to be both feasible and effective in the prehospital setting.

Adult↗

[Temporomandibular joint morphology and morphometric findings in relation to degree of disk displacement. Comparative magnetic resonance tomography studies].

In order to evaluate magnetic resonance imaging (MRI) changes in correlation with different degrees of internal derangement of the temporomandibular joint, we evaluated 117 joints of 59 symptomatic patients and 31 volunteers. Data analysis included morphologic and morphometric characteristics. Sixteen joints (19%) were considered normal, 40 demonstrated anterior displacement with reduction (47%) and 27 anterior displacement without reduction (32%). In three of the volunteers anterior displacement with reduction was noted. Advancing anterior position of the disk was associated with reduced ability to open the mouth, progressive deformity and shortening of the disk, thinning of the bilaminar zone, regressive and proliferative bony changes of the condyle, reduced translatory movement of the disk and condyle, thinning of joint space, cranial and dorsal displacement of the condyle and flattening of the slope of the tuberculum. In addition to alterations in condylar and disk morphology, MRI can demonstrate various additional measurable changes that correlate well with the degree of anterior disk displacement.

Adult↗

Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gram-negative sepsis.

OBJECTIVE: The evaluation of incidences and relating factors of severe persisting critical illness polyneuropathy (CIP) in survivors of multiple organ failure (MOF). DESIGN: Prospective study with an entry period of 24 months. Electrophysiological studies for the diagnosis of CIP were performed 1 or 2 days before the patients were discharged from the intensive care unit (ICU). Factors which might have been related to the development of CIP were identified by a retrospective chart analysis. SETTING: The interdisciplinary ICU of a university hospital. PATIENTS: Thirty-three patients who survived MOF. Sixteen of these critically ill patients developed severe sepsis due to nosocomial infections with gram-negative bacteria. RESULTS: In seven survivors of MOF and sepsis typical electrophysiological features of CIP, like spontaneous fibrillations and low compound muscle action potentials, were detectable at the time of discharge from the ICU. Seventeen patients with MOF following multiple trauma who developed no sepsis, and nine survivors of MOF with sepsis showed no signs of persisting CIP at the end of their ICU stay. Chart analysis revealed that eight survivors of MOF with sepsis and without the development of CIP had been treated with intravenous immunoglobulin (IVIG) with a dosage of 0.3 g/kg per day for 3 days immediately (within 24 h) after the diagnosis of sepsis. Four out of seven patients with MOF and sepsis who developed CIP were transferred to our ICU after the onset of sepsis and had not received IVIG treatment. The IVIG treatment in three patients was delayed for more than 24 h after the diagnosis of sepsis and was then omitted. Obviously not related to the development of CIP were aminoglycoside antibiotics, steroids, nutritional disturbances and episodes of hypotension or hypoxia. Neuromuscular blocking agents were not used during intensive care treatment. CONCLUSIONS: A high incidence of severe CIP persisting until the day of discharge from the ICU was related to gram-negative sepsis but not to MOF alone. Retrospective chart analysis suggested that early application of IVIG may prevent or mitigate this severe complication. However, these results have to be confirmed in a prospective, placebo-controlled study.

APACHE↗

Light and electron microscopy study of carbohydrate antigens found in the electron-lucent layer of Pneumocystis carinii cysts.

The localization and biochemical nature of antigens found in the electron-lucent layer (ELL) of Pneumocystis carinii cysts using polyclonal rabbit antibodies are described. These antigens, specific for the cystic stages of the parasite, were shared by organisms from different hosts, suggesting that they represent functionally important components of the cyst cell wall. The binding sites were situated on an interwoven net of fibrils in the ELL produced by mild to strong proteolysis. Degradation of this residue by glucanase and chitinase confirms that this layer contains branched glucan and chitin. In contrast, the prompt susceptibility of the polysaccharide-rich ELL to proteolysis reveals that proteins are also relevant in building up the cyst-wall glucan skeleton. It is therefore concluded that the formation of the Pneumocystis cyst wall shows differences to the typical fungal cell-wall architecture. The taxonomical debate regarding this unique protist is ongoing, and consideration of these immunological and morphological findings may be useful for the study of the biology and phylogeny of Pneumocystis.

AIDS-Related Opportunistic Infections↗

The Memorial Delirium Assessment Scale.

We conducted two studies with medically hospitalized cancer and acquired immunodeficiency syndrome (AIDS) patients to assess the reliability and validity of a new measure of delirium severity, the Memorial Delirium Assessment Scale (MDAS). The first study used multiple raters who jointly administered the MDAS to 33 patients, 17 of whom met DSM III-R/DSM IV criteria for delirium, 8 met diagnostic criteria for another cognitive impairment disorder (for example, dementia), and 8 had non-cognitive psychiatric disorders (for example, adjustment disorder). Results indicate high levels of inter-rater reliability for the MDAS (0.92) and the individual MDAS items (ranging from 0.64 to 0.99), as well as high levels of internal consistency (coefficient alpha = 0.91). Mean MDAS ratings differed significantly between delirious patients and the comparison sample of patients with other cognitive impairment disorders or no cognitive impairment (P < 0.0002). The second study compared MDAS ratings of 51 medically hospitalized delirious patients with cancer and AIDS made by one clinician to ratings on several other measures of delirium (Delirium Rating Scale, clinician's ratings of delirium severely) and cognitive functioning (Mini-Mental State Examination) made by a second clinician. Results demonstrated a high correlation between MDAS scores and ratings on the Delirium Rating Scale (r = 0.88, p < 0.0001), the Mini-Mental State Examination (r = -0.91, P < 0.0001), and clinician's global ratings of delirium severity (r = 0.89, P < 0.0001). Thus, our findings indicate that the MDAS is a brief, reliable tool for assessing delirium severity among medically ill populations that can be reliably scored by multiple raters. The MDAS is highly correlated with existing measures of delirium and cognitive impairment, yet offers several advantages over these instruments for repeated assessments which are often necessary in clinical research.

Adult↗

Submillisecond AMPA receptor-mediated signaling at a principal neuron-interneuron synapse.

Glutamatergic transmission at a principal neuron-interneuron synapse was investigated by dual whole-cell patch-clamp recording in rat hippocampal slices combined with morphological analysis. Evoked EPSPs with rapid time course (half duration = 4 ms; 34 degrees C) were generated at multiple synaptic contacts established on the interneuron dendrites close to the soma. The underlying postsynaptic conductance change showed a submillisecond rise and decay, due to the precise timing of glutamate release and the rapid deactivation of the postsynaptic AMPA receptors. Simulations based on a compartmental model of the interneuron indicated that the rapid postsynaptic conductance change determines the shape and the somatodendritic integration of EPSPs, thus enabling interneurons to detect synchronous principal neuron activity.

Animals↗

Distinct agonist-mediated endocytosis of cloned rat somatostatin receptor subtypes expressed in insulinoma cells.

Endocytosis of somatostatin receptors could regulate cellular responses to the two natural peptides, somatostatin-14 and somatostatin-28, and to synthetic ligands used in the clinical diagnosis and symptomatic therapy of neuroendocrine tumours. The five cloned SSTRs with or without epitope tags at their carboxyl-termini were expressed in rat insulinoma 1046-38 cells. Application of the two natural peptides or octreotide, at 37 degrees C but not at 4 degrees C, to cells transfected with somatostatin receptor subtype 2 or 3 cDNA resulted in a significant decrease of cell surface binding-sites for 125I-Tyr11-somatostatin-14. In contrast, cells transfected with subtype 5 cDNA only responded to stimulation with octreotide or somatostatin-28. Cells transfected with subtype 1 cDNA responded to somatostatin-14 and 28, while cells expressing subtype 4 cDNA showed no response. Confocal microscopy revealed that 6 min after stimulation with somatostatin-14 at 37 degrees C, tagged somatostatin receptor subtypes 1, 2 and 3 were internalized into vesicles. Internalization was not observed at 4 degrees C in the presence of 0.4 M sucrose and 80 microM phenylarsine oxide and hence proceeded via endocytosis through clathrin-coated pits and vesicles. After 20 min the internalized receptors appeared in perinuclear vesicles and after 120 min they reappeared at the plasma membrane. This recycling was not sensitive to cycloheximide and, hence, not dependent on de novo protein synthesis. Recovery of cell surface receptors was, however, inhibited by brefeldin A, monensin and bafilomycin A1, indicating that receptor recycling proceeded through vesicular traffic of acidified compartments. The data are consistent with the assumption that the observed agonist and subtype specific internalization of somatostatin receptors in a neuroendocrine cell line may be important for tumour diagnosis and therapy and, thus, suggest a manifold control in cellular signalling.

Adenylyl Cyclases↗

[Stimulation parameters for automatic examination of color vision].

PURPOSE: We have developed a polyvalent computer controlled instrument, which uses the "two equation method" (Rayleigh and Moreland equations) to measure human colour vision. This "colorimeter" (or anomaloscope) was used to determine the influence of some important stimulation parameters. METHODS: The influence of stimulus exposure time, observation field size, absolute stimulus luminance, saturation and luminance mismatches between mixture and reference stimuli were measured on our computer controlled colorimeter. All subjects were normal observers. RESULTS: 1) An exposure time of 2s was found to be optimal for clinical work. 2) The Moreland equation on a 7 degrees observation field yields results in which population variability is comparable to a Rayleigh equation on a 2 degrees field. 3) A retinal illuminance between 40 and 1000 trolands can be used for automated Moreland matches. 4) The saturation of the reference field for the Moreland match can be preset to a fixed value. 5) It is important to vary automatically the radiance of the reference field to provide an approximate luminance match as the ratio of primaries in the mixture field is changed. CONCLUSION: These measurements allows us to determine optimal conditions for automated colour vision examinations and to make recommendations for an international standard.

Color Perception Tests↗

Endocytosis of the rat somatostatin receptors: subtype discrimination, ligand specificity, and delineation of carboxy-terminal positive and negative sequence motifs.

Endocytosis of the five rat somatostatin receptor subtypes (SSTR1-5) was investigated in transfected HEK cells by biochemical ligand binding assays and confocal microscopic analysis. Phenylarsine oxide-sensitive internalization of SSTR1-3 is dependent on SST-14 or SST-28, whereas only the octacosapeptide triggers this reaction with SSTR5. SSTR4 is not internalized with either SST. Internalized SSTR3 is cycled back to the plasma membrane while endocytosed rho-Ala1-SST-14 remains inside the cell. Delineation of sequence motifs responsible for internalization of SSTR3 revealed multiple serines and a threonine (Ser-341, Ser-346, Ser-351, and Thr-357) within the carboxy-terminal tail of which Ser-351 and Thr-357 were the most effective ones. Chimeras in which various segments of the carboxyl terminus of SSTR4 were replaced by the corresponding regions of SSTR3 were internalized as long as they contain the Ser/Thr motif. However, this internalization reaction was suppressed when the chimeras were extended by the carboxyl terminus of SSTR4 (residues 320-384), suggesting the presence of a negative control element in that region. Step-wise truncation of the carboxyl terminus of wild-type SSTR4 revealed a motif of three amino acid residues Glu-Thr-Thr (SSTR4-330-332) that is responsible for preventing internalization and may be important in regulating endocytosis of this receptor subtype.

Amino Acid Sequence↗

A multicenter study of recombinant human erythropoietin (epoetin alpha) in the management of anemia in cancer patients receiving chemotherapy.

Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p < 0.0001) improvement in mean WHO performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.

Adolescent↗

The CB-12L: a new device for transtelephonic transmission of a 12-lead electrocardiogram.

The value of transtelephonic transmission of ECG information is well established, and technological advances have continuously provided improved state-of-the-art equipment. Shahal Medical Services provides professional care to subscribers who call the medical center and describe their symptoms, whereupon therapeutic measures are decided upon. A new 12-lead patient controlled device for telephonically transmitting an ECG (GB-12L) has become available; the aim of this study was to evaluate its accuracy and practicability. Forty tracings (20 standard ECG tracings obtained under medical supervision in the physician's office and 20 by the patient in his home using the new CB-12L ECG device and transmitted by telephone to the center) from 20 subjects with various electrocardiographic pathologies were reviewed by 19 experienced physicians who were asked to interpret the results and identify the recording device. In 82% of the possibilities, the interpretation of the tracings was identical for both those recorded by the standard ECG recorder and the CB-12L ECG. An equal number of physicians could not identify the means by which device the tracings were taken. Proper placement of the electrodes did not prove to be a problem for the patient. Thus, the CB-12L ECG was found to be an easily operable and reliable tool which may be of value for early and prompt diagnosis of threatening cardiac situations in the prehospital setting.

Electrocardiography↗

Tuning of electroreceptors in the blind cave salamander, Proteus anguinus L.

The blind cave salamander's (Proteus anguinus L.) sensitivity for electrical fields was determined by recordings from afferent fibers coming from ampullary electroreceptors. The animals were stimulated with single rectangular or continuous sinusoidal electrical signals passed through the cave water in the experimental tank. Best threshold sensitivities of the fibers for both kinds of signals were in the same range (0.1-0.5 mV/cm = 30-150 nA/cm2). The fibers showed phase-locked responses to rostrally cathodic phases of rectangular or sinusoidal stimuli and suppression to anodal phases. Units were tuned to 'best frequencies' (B.F., sine waves) between 20 and 40 Hz. Any functional, i.e. phase-related, firing or suppression of firing occurs in a total frequency range of less than 0.1 to around 100 Hz. This frequency range of tuning in the primary fibers was the same as found in the behavior, and this therefore reflects the peripheral sensory properties. Electrical sensitivity might be of special value for these cave dwelling animals, as they may detect and recognize prey animals by means of the prey's electrical field spreading into the surroundings, i.e. its electromyogram.

Afferent Pathways↗

Molecular diagnosis of tuberculosis: current clinical validity and future perspectives.

The rapid development and availability of a variety of new molecular genetic technologies present the clinician with an array of options for the accurate diagnosis of infectious diseases. This is particularly the case for tuberculosis, since molecular methods have been rapidly introduced into all working areas of the mycobacteriology laboratory. Nucleic acid amplification methods to detect Mycobacterium tuberculosis in clinical specimens are increasingly used as a tool to diagnose tuberculosis. The bulk of recently available data from clinical evaluations performed under routine laboratory conditions indicate that these molecular methods are rapid and sensitive, but yet inferior, to culture with regard to sensitivity and specificity. Therefore, until gene amplification tests have proved to be reliable and quality control procedures exist, their clinical validity remains controversial. Consequently, definition of selected clinical applications of gene amplification to routine diagnosis of tuberculosis is important and need to be discussed. This review will focus on the clinical role of molecular methods in the direct detection and diagnosis of M. tuberculosis in clinical samples. In addition, molecular genetic approaches designed to determine drug susceptibility and to discriminate strains below the species level will be outlined and discussed in terms of their current and future clinical applicability.

DNA Fingerprinting↗

Telemedicine in emergency home care--the 'Shahal' experience.

Shahal serves over 40,000 cardiac, pulmonary and blood pressure subscribers. The system combines emergency home care and telemedicine in a patient-initiated system geared towards the prevention of cardiac and pulmonary complications. About 150,000 calls are received per year. The median time from onset of symptoms to a call for help is 44 min. It is a unique system which has been shown to facilitate improved home health-care control, enabling patients to manage their own health condition and providing them with a higher quality of life and enhanced peace of mind.

Adolescent↗

Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.

Acquired Immunodeficiency Syndrome↗