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[The potentials and limits of the radiotherapy of laryngeal carcinoma].

Early stage glottic carcinoma can be treated with primary radiotherapy reaching equally good results compared to primary surgery; for supraglottic carcinoma surgery offers only slight advantages over primary radiotherapy. Tumor control for recurrences is considerably improved by salvage surgery. The use of primary radiotherapy allows improved or at least preserved voice and reduced rates of acute complications and late treatment sequelae. However, treatment duration is longer and probably more expensive compared to function preservation microlaryngoscopic surgery. Which treatment approach is chosen, depends on individual patient factors and specific conditions in the clinical setting. In any case, primary radiotherapy deserves a stronger say in the early stage tumor situation. In our institution early stage supraglottic carcinomas undergo primary surgery. Advanced carcinomas (T2b and more) are rarely suited for primary radiotherapy with the exception of some very confined T3 tumors. Surgical approaches should be favoured, since they provide a detailed pathohistological tumor staging including R-classification, which would be lacking using primary radiotherapy. There are clear reasons to treat the lymph nodes for glottic carcinomas stage T2b and more and for all supraglottic carcinomas with radiotherapy. Specific risk factors are: tumor at the margins of the incision (R1), infiltration of the cartilage and pre-epiglottic space, paratracheal and subglottic extension of more than 1 cm, perineural invasion, grade III and IV as well as emergency tracheostomy. Postoperative radiotherapy should be given to the lymph nodes for all positive neck-dissections. New therapeutic approaches are on the horizon, which may improve the results of radiotherapy even for advanced larynx carcinomas, like hyperfractionation radiotherapy and simultaneous radio-chemotherapy combined enoral resection and postoperative radiotherapy may yield larynx preservation even for advanced stages. New imaging techniques allow an improved staging and predictive radiobiological assays may play a major role in tumor prognosis.

Carcinoma↗

Properties of spike train spectra in two parietal reach areas.

In the lateral intraparietal area (LIP), a saccade-related region of the posterior parietal cortex (PPC), spiking activity recorded during the memory period of an instructed-delay task exhibits temporal structure that is spatially tuned. These results provide evidence for the existence of 'dynamic memory fields' which can be read-out by other brain areas, along with information contained in the mean firing rate, to give the direction of a planned movement. We looked for evidence of dynamic memory fields in spiking activity in two parietal reach areas, the parietal reach region (PRR) and area 5. Monkeys made center-out reaches to eight target locations in an instructed-delay task with a memory component. Neurons in both areas exhibited sustained activity during the delay period that was spatially tuned. Many single cell PRR spectra exhibited spatially tuned temporal structure, as evidenced by a significant and spatially tuned peak in the 20-50 Hz band. The PRR population spectrum of spike trains was also tuned, with the peak power centered on approximately 25 Hz. In contrast, area 5 spiking activity did not exhibit any significant temporal structure. These results suggest that different mechanisms underlie sustained delay period activity in these two areas and that dynamic memory fields, as revealed by our techniques, are more prominent in PRR than in area 5. Temporal structure in the spike train and local field potential (LFP) are related in at least one other brain area (LIP). The present results suggest then that LFP activity obtained from PRR may be better suited than area 5 LFP activity for use in neural prosthetic systems that incorporate analysis of temporal structure as part of a decode mechanism for extracting intended movement goals.

Action Potentials↗

Use of the Amplatzer Vascular Plug for embolization of a large retroperitoneal shunt during transjugular intrahepatic portosystemic shunt creation for gastric variceal bleeding.

A patient undergoing transjugular intrahepatic portosystemic shunt (TIPS) creation for gastric variceal hemorrhage was found to have a very large spontaneous splenorenal shunt requiring embolization after successful TIPS creation. The anticipated site of embolization was short and large in diameter and was therefore poorly suited for the use of conventional devices such as coils. Two Amplatzer Vascular Plugs and two platinum coils were used to occlude the shunt rapidly and completely.

Aged↗

The cochlear amplifier as a standing wave: "squirting" waves between rows of outer hair cells?

This paper draws attention to symmetric Lloyd-Redwood (SLR) waves-known in ultrasonics as "squirting" waves-and points out that their distinctive properties make them well-suited for carrying positive feedback between rows of outer hair cells. This could result in standing-wave resonance-in essence a narrow-band cochlear amplifier. Based on known physical properties of the cochlea, such an amplifier can be readily tuned to match the full 10-octave range of human hearing. SLR waves propagate in a thin liquid layer enclosed between two thin compliant plates or a single such plate and a rigid wall, conditions found in the subtectorial space of the cochlea, and rely on the mass of the inter-plate fluid interacting with the stiffness of the plates to provide low phase velocity and high dispersion. The first property means SLR wavelengths can be as short as the distance between rows of outer hair cells, allowing standing wave formation; the second permits wide-range tuning using only an order-of-magnitude variation in cochlear physical properties, most importantly the inter-row spacing. Viscous drag at the two surfaces potentially limits SLR wave propagation at low frequencies, but this can perhaps be overcome by invoking hydrophobic effects.

Basilar Membrane↗

Rats with scopolamine- or MK-801-induced spatial discrimination deficits in the cone field task: animal models for impaired spatial orientation performance.

Spatial cognition appears to be compromised in elderly and in patients suffering from dementia. These deficits are believed to be modelled, at least partly, by the administration of scopolamine or MK-801 in normal adult animals. In order to establish an animal model suited for the evaluation of putative cognition enhancers, we assessed the effects of scopolamine (0.3, 0.5, 0.7 mg kg(-1), i.p.) and MK-801 (0.07, 0.08, 0.09 mg kg(-1), s.c.) in rats trained in the cone field. This task allows the simultaneous investigation of working memory (WM), reference memory (RM) and search strategies. Scopolamine and MK-801 reliably induced spatial cognition deficits in the cone field without inducing behavioural side effects. This task appears to be suited for assessing the effects of putative cognition-enhancing compounds on spatial cognition.

Animals↗

Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest.

BACKGROUND: Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights. METHODS: For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR. RESULTS: After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION: The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.

Adult↗

Human cardiovascular and vestibular responses in long minutes and low +Gz loading by short arm centrifuge.

1.4 G, 1.7 G, and 2.0 G of +Gz and 60 minutes centrifugation was adopted to 20 healthy male subjects using 1.8 m radius centrifuge equipped to Nihon University School of Medicine. G was applied from lower G, considering G training effect for the subjects. Effects on performance decline and side effects of such a short-arm centrifugation were especially observed in the experiments, because this size of centrifuge could be used in space station in future for a strong countermeasure of cardiovascular deconditioning, demineralization from bone, etc. G training effect was observed same as higher and rapid G acceleration in fighter pilot. Subjects suffered from many types of discomfort; such as sensation of heaviness of diaphragm, cold sweat, nausea, irritable feeling, arrhythmia, tachycardia, rapid decrease of blood pressure, which sometimes caused interruption of G load. As 2.0 G and 60 minutes centrifugation seemed very tough load to the subjects, there should be necessary some G suit or other countermeasure, if we apply a higher G and/or longer G duration. Performance decline due to the load commonly continued for 1 hour or so. Side effects were observed in relation to neuro-vestibular, cardio-vascular, and autonomic nervous system.

Adult↗

Hemodynamic effects of intrathecal fentanyl in nonlaboring term parturients.

STUDY OBJECTIVE: To determine the effect of intrathecal fentanyl on maternal hemodynamics. DESIGN: Prospective. SETTING: Labor and delivery suite of a university medical center. PATIENTS: 23 ASA status I nonlaboring term parturients presenting for elective cesarean section. INTERVENTIONS: Patients were given either 1,200 ml lactated Ringer's Solution (Group 1, n = 12) or no intravenous (i.v.) fluid (Group 2, n = 11). A combined spinal-epidural technique was then performed. Fentanyl 25 micrograms was administered intrathecally through a 24-gauge Sprotte or 25-gauge Whitacre spinal needle. After completion of the hemodynamic study, a catheter was threaded into the epidural space for local anesthetic administration. MEASUREMENTS AND MAIN RESULTS: Baseline hemodynamic data [systolic (SBP), diastolic, and mean arterial pressure, heart rate, stroke volume, cardiac output, end-diastolic volume, and ejection fraction] were obtained in triplicate using noninvasive blood pressure monitoring and impedance cardiography. After administration of intrathecal fentanyl, hemodynamic measurements were recorded at 3-minute intervals for 30 minutes. These values were compared with baseline for both groups. Ten patients in each group completed the study. Intrathecal fentanyl administration did not result in any maternal hemodynamic changes in Group 1, and a few small statistically significant changes in Group 2. Measured SBP was always greater than 100 mmHg in all patients during the study. CONCLUSION: Intrathecal administration of fentanyl 25 micrograms in nonlaboring term parturients does not produce clinically important maternal hemodynamic changes.

Adult↗

Intraoperative surgical specimen evaluation: frozen section analysis, cytologic examination, or both? A comparative study of 206 cases.

Having recently become aware of the merits of cytologic preparations, histopathologists are focusing their attention on cytologic examination as a means of intraoperatively evaluating surgical specimens. This study compares the diagnostic accuracy and quality of frozen-section (FS) and cytologic preparations from 206 surgical specimens. The quality of cytologic preparations was significantly superior to that of FSs (P = 0.0001). With the use of a three-level accuracy scale suited to the practical demands of intraoperative evaluation, there was no significant difference between the accuracy of diagnosis by FS analysis compared with that achieved by cytologic examination (P = 0.35). More importantly--except in one case--whenever one technique did not correctly distinguish benign from malignant disease, the other technique yielded an essentially correct diagnosis. With the use of both techniques, 99.5% of cases were interpreted correctly, at least in regard to benign versus malignant diagnoses. Because significant additional time, equipment, stains, laboratory space, or personnel are not needed to implement intraoperative cytologic studies in a routine anatomic pathology laboratory, the authors advocate the simultaneous use of FS and cytologic studies in the specified context.

Diagnostic Errors↗

Simultaneous detection and fine mapping of quantitative trait loci in mice using heterogeneous stocks.

We describe a method to simultaneously detect and fine map quantitative trait loci (QTL) that is especially suited to the mapping of modifier loci in mouse mutant models. The method exploits the high level of historical recombination present in a heterogeneous stock (HS), an outbred population of mice derived from known founder strains. The experimental design is an F(2) cross between the HS and a genetically distinct line, such as one carrying a knockout or transgene. QTL detection is performed by a standard genome scan with approximately 100 markers and fine mapping by typing the same animals using densely spaced markers over those candidate regions detected by the scan. The analysis uses an extension of the dynamic-programming technique employed previously to fine map QTL in HS mice. We show by simulation that a QTL accounting for 5% of the total variance can be detected and fine mapped with >50% probability to within 3 cM by genotyping approximately 1500 animals.

Animals↗

A modified posterolateral approach to the thoracic spine.

We describe a modified technique for posterolateral approach to the thoracic spine and report the use of this procedure in 21 patients. The technique is safe and effective for selected indications. The evolution of the posterolateral or costotransversectomy approach to the thoracic spine has in large part focused on enlarging the exposure to the vertebral bodies and epidural space by resecting an increasing number of ribs and removing a wider portion of those ribs resected. In this modified approach to the thoracic spine, the costovertebral articulation is preserved, and no rib resection is necessary to gain adequate exposure to the thoracic vertebral body and epidural space. We did a retrospective review of 21 patients undergoing 22 modified posterolateral approaches to the thoracic spine. Sixteen patients had biopsies of thoracic vertebral lesions through this approach; 3 underwent decompression of the thoracic spinal cord; 2 approaches were done for the removal of a herniated thoracic disc; and in one, the pedicle was removed. This modified posterolateral approach allowed adequate exposure for selected indications. One complication, a wound infection, developed after biopsy for suspected osteomyelitis. This modified posterolateral approach is well suited to provide access for biopsy of thoracic spinal lesions; for decompression of a paraspinal abscess; and for decompression of the thoracic spinal cord by anterolateral compressive lesions such as herniated thoracic disc or epidural tumor when resection of the vertebral body is not necessary; or the approach may be used for patients who are debilitated or at poor risk to undergo thoracotomy.

Adult↗

Identification of a low-risk subset of patients with stage IB invasive squamous cancer of the cervix possibly suited to less radical surgical treatment.

Because of the well-documented morbidity of radical hysterectomy, it would appear desirable to isolate a subset of patients at low risk of parametrial spread or disease recurrence who might thereby be candidates for less radical surgical therapy. To this end, the records of all patients undergoing radical hysterectomy for cervical carcinoma at our institution between 1956 and 1985 were reviewed. Of the 387 patients treated for squamous carcinoma clinically confined to the cervix, 83 (21.4%) had tumors with depth of invasion greater than 3 mm (stage IB) but volume of tumor less than or equal to that of a sphere 2 cm in diameter (4.19 cm3) and no tumor in angiolymphatic spaces. Of the 83 patients, none had parametrial nodal metastasis. Median follow-up of this subgroup was 9.8 years, and the Kaplan-Meier estimate of 5-year disease-free survival was 97.6% (95% confidence interval, 94.3-100%). We consider patients in the subset described above to be candidates for modified radical hysterectomy and pelvic lymphadenectomy, with a decrease in morbidity associated with the less radical dissection, a low risk of failure to excise occult parametrial tumor, and the expectation of an excellent chance of long-term disease-free survival.

Adult↗

Invasive aspergillus infection: possible non-ward common source within the hospital environment.

Six immunocompromised patients housed in widely separated portions of a hospital campus developed invasive aspergillosis during a single month. This represented a significant increase (P less than .001) in the number of cases observed over the 3 years which included this event (19 cases in 36 months). Epidemiological investigation suggested that this cluster of cases was due to a common source outbreak related to construction activity in a central radiology suite serving the hospital. Such non-ward exposures to nosocomial hazards are becoming increasingly important for immunosuppressed hosts.

Adult↗

A dedicated internal standard in fragment length analysis of hyperpolymorphic short tandem repeats.

Some of the most polymorphic short tandem repeats (STRs) have alleles differing in size by as little as one basepair. Since sizing precision with commercially available internal standards ordinarily does not allow safe discrimination at this level, typing is accomplished through comparisons with allelic ladders run on each gel. Here we introduce the use of optimally spaced sequenced alleles as a dedicated internal standard for measurement and typing of hyperpolymorphic STRs. We have constructed such a dedicated internal standard for HUMACTBP2 ([1]; Moos and Gallwitz, EMBO I., 5 (1983) 757-761) typing, including 25 sequenced, ROX labelled HUMACTBP2 alleles spanning the size range for alleles at this locus (233-333 basepairs (bp)). Comparisons of inter-gel runs of selected alleles with this dedicated standard and the commercial GS500 internal standard demonstrate that only the presently described internal standard is suited for direct typing based on fragment length measurements only. Obvious advantages of this typing procedure are that fragment measurements are precise and in accordance with sequenced lengths, and that the typing procedure via an external allelic ladder is avoided. Sequences of the alleles used in the internal standard as well as of selected alleles for allelic ladders in two other hyperpolymorphic AAAG-repeat STRs, D11S554 (Phromchotikul et al., Hum. Mol. Genet., 3 (1991) 21) and HUMAPOA11 (Kimpton et al., PCR Methods Appl., 3 (1993) 13-22) are also presented. To allow fragment length analysis of these two STRs, five D11S554 alleles, spanning from 176 to 225 basepairs, were added to the dedicated internal standard. Performing similar comparisons as for HUMACTBP2, it is demonstrated that even if sizing accuracy is not as good as with HUMACTBP2, typing based on measured fragment size only may be achieved with both other STRs as well. Selecting different colours for the three STRs, triplex electrophoretic runs were performed of a Norwegian population database of 300 unrelated individuals. The probability that two unrelated individuals have the same type in all three STRs is 5 x 10(-7), and the combined paternity exclusion power 99.77%, indicating that this STR selection may represent a good choice for forensic genetic casework.

Base Composition↗

Capillary ultrafiltration: in vivo sampling probes for small molecules.

Capillary ultrafiltration is a novel sampling method convenient for low molecular weight substances in living biological systems. By application of a negative pressure across a hydrophilic membrane capillary, small molecules are actively "pulled" across the membrane and collected. By elimination of large molecules and cellular matter, the ultrafiltrate collected is well suited for further analysis by liquid chromatography, capillary electrophoresis, or mass spectrometry. Ultrafiltration probes (UF probes) provide a simple means to obtain a small-volume sample from subcutaneous tissue, blood, saliva, or any other biological fluid in vivo. The dependence of recovery on flow rate, temperature, membrane dimensions, and vacuum magnitude are considered. The relative merits of capillary ultrafiltration probes and microdialysis probes are considered. UF probe applications presented include in vivo monitoring of drug disposition in human saliva and in the subcutaneous space of awake, freely moving rats.

Acetaminophen↗

CADLIVE for constructing a large-scale biochemical network based on a simulation-directed notation and its application to yeast cell cycle.

The further understanding of the mechanisms of gene regulatory networks requires comprehensive tools for both the representation of complicated signal transduction pathways and the in silico identification of genomic signals that govern the regulation of gene expression. Consequently, sophisticated notation must be developed to represent the signal transduction pathways in a form that can be readily processed by both computers and humans. We propose the regulator-reaction equations combined with detailed attributes including the associated cellular component, molecular function, and biological process and present the simulation-directed graphical notation that is derived from modification of Kohn's method. We have developed the software suite, CADLIVE (Computer-Aided Design of LIVing systEms), which features a graphical user interface (GUI) to edit large-scale maps of complicated signal transduction pathways using a conventional XML-based representation. The regulator-reaction equations represent not only mechanistic reactions, but also semantic models containing ambiguous and incomplete processes. In order to demonstrate the feasibility of CADLIVE, we constructed a detailed map of the budding yeast cell cycle, which consists of 184 molecules and 152 reactions, in a really compact space. CADLIVE enables one to look at the whole view of a large-scale map, to integrate postgenomic data into the map, and to computationally simulate the signal transduction pathways, which greatly facilitates exploring novel or unexpected interactions.

Cell Cycle↗

Capillary effects in a confined smectic phase of hard spherocylinders: influence of particle elongation.

A system of hard rods confined into a pore with slit geometry (two parallel planar substrates) is studied theoretically in the regime of high packing fraction. In this regime the bulk system exhibits a nematic phase as well as a smectic-A (spatially layered) phase. When the system is confined, strong commensuration effects between the layer spacing and the pore width bring about a rich phenomenology, with a phase diagram showing layering and capillary transitions. The latter include capillary smectization transitions whereby a confined smectic phase occurs at conditions of saturation different from those of the corresponding bulk fluid. These transitions are seen to be intimately connected with layering transitions involving discontinuous changes in the number of layers inside the pore. This rich phenomenology is obtained by use of a sophisticated density-functional, Onsager-theory-based approach, especially suited to deal with strongly inhomogeneous fluids. The theory allows for a unified description of ordering and phase behavior of the fluid in confined geometry, and permits us to correlate the above behavior with the wetting properties of the fluid on a single substrate.

Journal Article↗

Competition for neurotrophic factors: mathematical analysis.

Neurotrophic factors, particularly the neurotrophin gene family of neurotrophic factors, are implicated in activity-dependent anatomical plasticity in the visual cortex and at the neuromuscular junction. Accumulating evidence implicates neurotrophic factors as possible mediators of activity-dependent competition between afferents, leading to the segregation of afferents' arbors on the target space. We present a biologically plausible mathematical model of competition for neurotrophic factors. We show that the model leads to anatomical segregation, provided that the levels of neurotrophic factors released in an activity-independent manner, or the levels available by exogenous infusion, are below a critical value, which we derive. Above this critical value, afferent segregation breaks down. We also show that the model segregates afferents even in the presence of very highly correlated patterns of afferent activity. The model is therefore ideally suited for application to the development of ocular dominance columns in the kitten visual cortex.

Afferent Pathways↗