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We present evidence that catecholamines, which are commonly used to stimulate lipolysis in adipose tissue in vitro, interfere with the enzymatic determination of non-esterified fatty acid (NEFA) in two commercially available kits. Measurement of a 100 mumol/L standard with the Wako "NEFA C" test kit was 60% inhibited by 100 mumol/L norepinephrine and was completely inhibited by 100 mumol/L isoproterenol or by 1 mmol/L norepinephrine or epinephrine. Measurement with the Boehringer Mannheim "Free Fatty acids, Half-micro test" was completely inhibited by 100 mumol/L norepinephrine and was also affected by concentrations as low as 0.1 mumol/L. We propose that this effect is due to the catecholamines interfering with a step common to the two kits, the generation of hydrogen peroxide and oxidation of a chromagen; furthermore, this interference appears to be stoichiometric. We also give details of an alternative in-house method, which does not depend on the generation of hydrogen peroxide and is not affected by catecholamines.

To compare local cone and rod system function in patients with retinitis pigmentosa (RP) using electrophysiological and psychophysical techniques.Cone-mediated multifocal electroretinograms (M-ERGs), cone system threshold visual fields, rod-mediated M-ERGs, and rod system threshold visual fields were measured in seven patients with RP.All the patients had normal cone system visual field thresholds and normal cone-mediated M-ERG implicit times within the central 5 degrees. Both cone-mediated responses were abnormal at some peripheral retinal locations. There were significant correlations among cone system amplitude, timing, and visual field loss. All the patients had some retinal areas where the rod-mediated M-ERG amplitudes were not measurable. In areas where they were measurable, these rod-mediated M-ERG responses were often within normal limits for amplitude and timing. In contrast to the cone system data, there were no significant relationships between rod-mediated M-ERG measures and rod system threshold elevations. The cone and rod system psychophysical thresholds showed regional correspondence; the amplitude-scale and time-scale measures of the M-ERG did not.The results indicate that there was better local correspondence between psychophysical and electrophysiological measures in the cone system than in the rod system in patients with RP. In addition, the psychophysical measures of cone and rod system function showed better correspondence than did the electrophysiological measures.

To assess the effects of focal photocoagulation on retinal function in the macular and perimacular areas in patients with diabetes who have clinically significant macular edema.Eleven patients were assessed after focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques were used to evaluate the effects of treatment on macular, paramacular, and peripheral retinal function. A modified visual field technique was used to obtain local threshold fields. The posttreatment results were compared with pretreatment results. Changes in local ERG response amplitudes and implicit times were calculated for each patient and presented as difference fields. The changes in local ERG responses were compared with the changes in local field sensitivity.After treatment, the results of the psychophysical tests suggested little or no change in visual function, but changes in retinal function were observed with the multifocal ERG technique. Local ERG responses showed increases in implicit time and decreases in amplitude, compared with pretreatment values. Timing was affected more than amplitude.The results suggest that focal treatment produces changes in retinal function, and these changes are not restricted to the treated macular area.

To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor-specific transcription factor.Heterozygotes with the E168 [delta1 bp], E168 [delta2 bp], or G217 [delta1 bp] CRXgene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT).Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [delta1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [delta2 bp], G217 [delta1 bp] mutations). In the family with the E168 [delta1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone-isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [delta1 bp] mutation) and two other patients (representing E168 [delta2 bp] and G217 [delta1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery.Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.

To determine whether the rod and cone photoreceptors are affected in patients with diabetic retinopathy.Twelve patients with diabetes and varying levels of retinopathy and nine age-similar control observers participated in this study. Two-color (500 versus 650 nm) dark-adapted thresholds were measured as a function of retinal eccentricity. Full-field flash electroretinograms were obtained using brief, high-intensity flashes. Dark-adapted rod-isolated (Wratten 47B filter) and light-adapted cone-isolated (Wratten 26 filter) electroretinographic responses were measured as a function of flash intensity. The a-wave data were fitted with a model based on photopigment transduction to obtain values for the parameters of Rmax (the maximal response) and log S (sensitivity). Standard clinical 30-Hz flicker electroretinographic responses were also measured.Psychophysically measured dark-adapted thresholds were elevated primarily at eccentricities of 5 degrees and 10 degrees from the fovea. Analysis of rod and cone a-wave data showed that Rmax was normal in most of the patients, but log S was reduced. Analysis of b-wave and oscillatory potential parameters showed rod and cone postreceptoral abnormalities, including changes in the rod-isolated semisaturation constant (log k), cone-mediated 30-Hz flicker, and cone-isolated oscillatory potentials. The electrophysiological results were not significantly correlated with blood glucose or glycosylated hemoglobin level.The results provide evidence for rod and cone receptoral and postreceptoral deficits in patients with diabetic retinopathy. The photoreceptor changes are primarily in the log S (sensitivity) parameter and are attributed to transduction abnormalities.

This pilot study compared biofeedback to increase respiratory sinus arrhythmia (RSA) with EMG and incentive inspirometry biofeedback in asthmatic adults. A three-group design (Waiting List Control n = 5, RSA biofeedback n = 6, and EMG biofeedback n = 6) was used. Six sessions of training were given in each of the biofeedback groups. In each of three testing sessions, five min. of respiratory resistance and EKG were obtained before and after a 20-min biofeedback session. Additional five-min epochs of data were collected at the beginning and end of the biofeedback period (or, in the control group, self-relaxation). Decreases in respiratory impedance occurred only in the RSA biofeedback group. Traub-Hering-Mayer (THM) waves (.03-.12 Hz) in heart period increased significantly in amplitude during RSA biofeedback. Subjects did not report significantly more relaxation during EMG or RSA biofeedback than during the control condition. However, decreases in pulmonary impedance, across groups, were associated with increases in relaxation. The results are consistent with Vaschillo's theory that RSA biofeedback exercises homeostatic autonomic reflex mechanisms through increasing the amplitude of cardiac oscillations. However, deep breathing during RSA biofeedback is a possible alternate explanation.

Many patients with retinitis pigmentosa (RP) show cone ERG b-waves that are depressed in amplitude and delayed in timing even during the early stages of RPe.g.1-3. Further, patients' photopic, visual fields measured with static perimetry show a range of losses in sensitivity both within and across patients4-7. Because of the difficulty in obtaining focal ERGs with conventional methods, little is known about the relationship of local sensitivity to local retinal activity outside the central retina. The multi-focal technique as described by Sutter and colleagues8,9 allows for simultaneous measurement of 103 focal retinal responses. Although a general agreement has been observed between visual field losses and multi-focal ERGs in patients with RP10-12, the relationship between local sensitivity changes and multi--focal ERG changes has yet to be explored. Here patients' multi-focal ERGs are compared to local visual field sensitivity measured with static perimetry.

The authors assessed airway impedance responses to psychological stressors among 113 individuals: 61 with asthma only (AS), 10 with asthma and panic disorder (ASPD), 24 with panic disorder only (PD), and 18 controls with neither condition (CON). Individuals with either AS or PD were affected by psychological stressors as measured by the forced oscillation technique. Individuals with PD (with or without AS) displayed lower airway impedance than those without PD. These data suggest that the airways of individuals with PD are in a chronic state of preparedness, which may promote hyperventilation.

Eighty-six asthmatics completed measures of illness-specific panic-fear (i.e., panic-fear in response to symptoms of asthma) and of generalized panic-fear, dyspnea frequency, and catastrophic cognitions about bodily symptoms (the Anxiety Sensitivity Index [ASI] and Agoraphobic Cognitions Questionnaire [ACQ]). Asthma variables (self-report and pulmonary function tests) and cognitive variables (ASI and ACQ) were independently related to illness-specific panic-fear. Regression analyses showed that the cognitive variables predicted significant variance in both panic-fear scales after controlling for the effects of demographic and asthma variables. By contrast, the asthma variables were not associated with generalized panic-fear when the cognitive measures were controlled. In light of the adverse effects of panic-fear on asthma, the authors' results suggest that researchers may fruitfully explore the use of cognitive techniques as an adjunctive treatment for improving asthma outcome.

We present evidence that catecholamines, which are commonly used to stimulate lipolysis in adipose tissue in vitro, interfere with the enzymatic determination of non-esterified fatty acid (NEFA) in two commercially available kits. Measurement of a 100 mumol/L standard with the Wako "NEFA C" test kit was 60% inhibited by 100 mumol/L norepinephrine and was completely inhibited by 100 mumol/L isoproterenol or by 1 mmol/L norepinephrine or epinephrine. Measurement with the Boehringer Mannheim "Free Fatty acids, Half-micro test" was completely inhibited by 100 mumol/L norepinephrine and was also affected by concentrations as low as 0.1 mumol/L. We propose that this effect is due to the catecholamines interfering with a step common to the two kits, the generation of hydrogen peroxide and oxidation of a chromagen; furthermore, this interference appears to be stoichiometric. We also give details of an alternative in-house method, which does not depend on the generation of hydrogen peroxide and is not affected by catecholamines.

Changes in body image across the menstrual cycle and the relationship between these changes and menstrual distress were investigated in an effort to identify determinants of body dissatisfaction. Twenty-six normally cycling women between 18-40 years of age and 90-115% of ideal body weight, with no history of an eating disorder, completed a series of body image measures and a measure of menstrual distress during three menstrual cycle phases: perimenstrual, follicular, and luteal. These phases were identified with serum levels of ovarian hormones and basal body temperature. Results indicated that body dissatisfaction as measured by the number of body-related negative thoughts and anxiety about appearance was significantly highest during the perimenstrual phase. In contrast, measures of body size perception remained stable. Several somatosensory and psychological symptoms of menstrual distress were significantly associated with body dissatisfaction during the perimenstrual phase including, water retention, autonomic reactivity, control, negative affect, and impaired concentration. This association of body dissatisfaction and menstrual distress strongly suggests that menstrual cycle changes play a significant role in body image.

Proposed binge eating disorder (BED) diagnostic criteria were investigated to provide necessary psychometric characteristics and explore their utility in assessment. One hundred four subjects (52 self-referred bingers, 52 comparison subjects) completed an initial administration of the Questionnaire of Eating and Weight Patterns (QEWP). The results supported the ability of the two core BED criteria (i.e., episodic overeating, loss of control) to discriminate between clinical and nonclinical binge eaters. Thirty-nine of the self-referred and 40 of the comparison subjects completed a second QEWP administration 3 weeks later. Results indicated that the BED diagnosis was moderately stable over the 3-week interval (kappa = .58, combined sample). Using self-monitoring data completed by the self-referred subjects, predictive efficiency analyses indicated that the QEWP was able to identify both high and low probability binge eaters. Implications of the findings for the definition, assessment, and utility of the BED diagnosis are discussed.

To study the effects of acetazolamide on central and peripheral visual function in patients with retinitis pigmentosa (RP) who showed no evidence of macular edema.Thirteen patients with retinitis pigmentosa participated in a preliminary study. Measures of central and peripheral visual function were obtained before and after an 8 wk period on acetazolamide. An additional 10 patients participated in a cross-over study. They were placed on a placebo for an 8 wk period, then on acetazolamide for a second 8 wk period.None of the patients in the preliminary study showed significant changes in visual acuity, color vision, foveal cone pathway sensitivities, focal electroretinogram (ERG) amplitudes, or in any ERG parameter. Three patients, however, showed significant changes in visual field area and in dark-adapted thresholds. None of the patients in the cross-over study showed significant increases in visual field area.Given the results and the reports of side-effects, it is difficult to justify using acetazolamide to improve retinal function in RP patients who show no evidence of cystoid macular edema.

e20514 Background: Radiotherapy improves local control after limb-sparing surgery for soft tissue sarcomas (STS). IMRT can optimize treatment dose conformity compared to standard conformal therapy. At the Northern Centre for Cancer Care we prescribe 60Gy. Until 2009 this was delivered using conventional Linac-based 3D conformal RT. Since installation of a tomotherapy unit, because of the potential long- term clinical advantages, selected sarcoma patients have been treated with postoperative IMRT. Tomotherapy necessitates longer planning, verification, and treatment times. These have been analysed to assess impact on resources. Methods: Six such patients have now been treated with IMRT. Tomotherapy planning requires more volume definition of organs at risk and “help structures” and processing for dose optimization. Times have been recorded within the implementation phase. Conventional Linac verification uses portal imaging daily for three days. Shifts are made to exclude systematic error, if tolerance is e...

SUMMARY Hypoglycaemia is associated with severe malaria and is an important prognostic indicator. Molecules liberated during overnight incubation of erythrocytcs infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with a delayed lime course compared with insulin: some, though weaker, activity could also be obtained by overnight incubation of uninfected crythrocytes. The active component shares many properties with (he phospholipid-containing molecules which we have previously shown to be toxic and to induce the release of tumour necrosis factor (TNF) from macrophages. However a MoAb which neutralizes the cytotoxicity of tumour necrosis factor in vitro did not prevent this induction of hypoglycaemia, whereas antiscrum against the toxic antigens did, as did immunization of normal (but not the immunoglobulin-deficient SCID) mice with the same material. Furthermore, normal mice injected with the antigens after immunization with phosphatidyl inositol or inositol monophosphale did not develop hypoglycaemia; the latter compound was also inhibitory when mixed with the antigens before injection. These compounds were previously shown to block the induction of TNF by the antigens and to induce the production of inhibilory antibodies. The role of these molecules in the etiology of the hypoglycaemia of malaria is discussed.

Four members of a family with dominantly inherited macular dystrophy demonstrated the essential features of hereditary hemorrhagic macular dystrophy. They reported decreased visual acuity in the third decade and eventually developed bilateral disease. Fundus evaluations revealed hemorrhagic and exudative maculopathy associated with pigment atrophy, pigment clumping, and eventual glial scar formation. Early stages of the disease manifested a macular subretinal neovascular network. Photocoagulation treatment of subretinal neovascularization was successful in Case 3, unsuccessful in Case 1. Follow-up of these four brothers lasted over a period of two to 12 years. After they reached the cicatricial phase, the size of the lesion and visual symptoms remained stable. Visual function tests in the early and late stages indicated a local or geographic disease. We differentiated this dystrophy from other hereditary causes for subretinal neovascularization. We recommend early obliteration of the subretinal neovascular network with intense photocoagulation because the outcome of untreated hereditary hemorrhagic macular dystrophy is legal blindness.

We discuss the use of synchronous-demodulation (lock-in) techniques for evoked potential retrieval. Application to electronically swept visual displays is emphasized. These techniques permit a visual threshold to be specified in 20 s, but their application to visual assessment requires careful consideration of several problems, notably alleged delay in the instrumentation, specification of the baseline response level, and the nature of EEG interference. In addition, since stimulus waveform information is lost in all lock-in methods, questions concerning what activity is contributing to the measured response must be answered. A technique addressing these issues and combining phase-sensitive detection and vector computation is presented.

2. The improper integral defined as the limit of a sum. We first consider the case where ak = 1 (k =1, 2, 3, * * * ). A fundamental difficulty not encountered in the previous paper is apparent from the definition of .fof(x)dx. Bromwich and Hardy have considered this problem [2]. As they point out, the ordinary definition of this improper integral is by means of a double (repeated) limit; and in order to replace this limit by the single limit

NASA and the Max Planck Institute for Extraterrestrial Physics (MPE), Munich, Germany, conducted a cooperative experiment involving the release and study of a barium cloud at 31,500 km altitude near the equatorial plane. The release was made near local magnetic midnight on Sept. 21, 1971. The MPE-built spacecraft contained a canister of 16 kg of Ba CuO mixture, a two-axis magnetometer, and other payload instrumentation. The objectives of the experiment were to investigate the interaction of the ionized barium cloud with the ambient medium and to deduce the properties of electric fields in the proximity of the release. An overview of the project is given to briefly summarize the organization, responsibilities, objectives, instrumentation, and operational aspects of the project.

A family with pseudoinflammatory macular dystrophy (PMD) is presented. This dominantly inherited macular dystrophy has its onset in the 3rd to 5th decades with the earliest manifestation being a macular subretinal neovascular network. Visual function tests (ERG, EOG, visual fields, retinal sensitivity) in the early and late stages indicates this is local or geographic disease. This dystrophy should be differentiated from other hereditary causes for subretinal neovascularization (angioid streaks, vitelliform dystrophy, dominant drusen of Bruch's membrane, optic nerve drusen and myopia). It is suggested that treatment be directed at early obliteration of the subretinal neovascularization with intense photocoagulation since the outcome in virtually all cases of untreated PMD is legal blindness.

Various noninvasive test procedures were used to evaluate retinal function in a patient who had become night blind following vincristine chemotherapy. The results obtained were strikingly similar to those reported previously in subjects with recessively inherited stationary night blindness; the dark-adaptation curve was monophasic (ie, no evidence of a scotopic branch), rhodopsin kinetics were entirely normal, and spectral threshold data revealed the presence of residual rod-mediated vision. Also like the heritable condition, the b-wave of the ERG was depressed grossly despite normal a-wave potentials. These findings, and the fact that vincristine is known to disrupt the structural integrity of neuronal microtubules, suggest that the drug-induced defect involves the process of synaptic transmission between the photoreceptors and their second-order neurons.

A psychophysical procedure, the probe-flash paradigm, was used to test explanations of early foveal sensitivity loss in retinitis pigmentosa. The findings suggest that this loss may be due to a decreased responsiveness of retinal elements and not to a decrease in quantum catching ability of functioning photoreceptors.

Two cases of testicular swelling associated with desipramine therapy are described. In one case, the swelling resolved with discontinuation of desipramine; in the other, the swelling subsided despite continuation and an increase in dose. These cases may represent a local variant of angioneurotic edema; however, further study is required to determine the exact etiologic mechanism.

We discuss the use of synchronous-demodulation (lock-in) techniques for evoked potential retrieval. Application to electronically swept visual displays is emphasized. These techniques permit a visual threshold to be specified in 20 s, but their application to visual assessment requires careful consideration of several problems, notably alleged delay in the instrumentation, specification of the baseline response level, and the nature of EEG interference. In addition, since stimulus waveform information is lost in all lock-in methods, questions concerning what activity is contributing to the measured response must be answered. A technique addressing these issues and combining phase-sensitive detection and vector computation is presented.

Multiple sclerosis can produce highly selective losses in visual function. Psychophysical studies have demonstrated contrast sensitivity deficits for spatial frequencies or for stimulus orientations. Using real-time lock-in retrieval of the visual evoked potential, the authors measured contrast sensitivity in 15 cases with probable or definite multiple sclerosis and acuities of 20/40 or better. Sine-wave grating contrast threshold determinations for three spatial frequencies (1, 4, and 8 cycles/deg) and four orientations (0, 45, 90, and 135 deg) revealed contrast deficits in at least one spatial frequency and orientation in every case. In most cases the visual losses were spotty or multifocal, and not the same in both eyes. Some cases with highly selective patterns of orientation or spatial frequency losses were observed and are discussed in terms of involvement of cortical functional architecture in the disease.

Electrophysiologic contrast sensitivity functions (CSF) have been estimated using lock-in amplifier signal retrieval of the visually evoked response (VER). These CSFs were compared with CSFs obtained psychophysically using the same stimulus conditions. The two measures of contrast sensitivity behave similarly in response to variations of temporal and spatial frequency. The major advantage of using real-time retrieval is speed. Threshold for a single spatiotemporal condition can be estimated in as little as 20 sec, making the application of electrophysiologic contrast sensitivity testing feasible for clinical populations.

A variety of retinal disease lead to a decrease in the sensitivity of the S (blue) cone pathways. To determine the possible sites and mechanisms of this loss we compared the sensitivities of an S (blue/pi-1) and an M (green/pi-4) cone pathway in patients with retinal diseases that differ as to their primary locus of sensitivity loss. The sensitivities of an S and an M cone pathway were assessed in patients with retinitis pigmentosa, insulin-dependent diabetes mellitus and open-angle glaucoma using Stiles two-color increment threshold technique. A greater loss in sensitivity of an S than an M cone pathway was found for all three disease groups; however, the diabetic patients showed a more selective loss. The results suggest that multiple sites are involved and that the combined effects of metabolic abnormalities and hypoxia contribute to the selective loss.

A stimulus consisting of 96 red LEDs mounted in the rear of a ganzfeld bowl was used to elicit focal electroretinograms (FERG) from the central 9 degrees of the retina in human subjects. The luminance of the stimulus was driven sinusoidally at frequencies from 10-60 Hz. The temporal responsiveness and response phase lags of normal subjects and patients with retinal disease were measured. Normal subjects produced maximum amplitude FERG responses to stimuli between 30-40 Hz. Patients with retinitis pigmentosa showed a low-pass pattern of amplitude loss, with an additional frequency independent loss in sensitivity in those with poorer visual acuity. Patients with macular degeneration showed general amplitude loss associated with a relative sparing of the mid-temporal frequencies. The response phase lags in both patient groups were not significantly different from the normals. These findings point to a loss in temporal responsiveness accompanied by a secondary loss of sensitivity in these heredoretinal degenerations.