The importance of electrode position in visual electrophysiology.

PURPOSE: The DTL fibre electrode is commonly used to record the electric potentials elicited by stimulation of the retina. Two positions are commonly used: it is placed either on the cornea along the lower lid or in the conjunctival fornix. The PERG and OPs have previously been examined and compared under both conditions. The aim of this study was to examine the ERG, flicker response and on-off responses with differing electrode positions. METHODS: Before recruitment, all subjects underwent an ophthalmological examination. We enrolled 13 normal control subjects into the study aged 13-64 years, all with a visual acuity of ≥1.0. We recorded scotopic and photopic ERGs, flicker and on-off responses, for both electrode positions. On the first day, one eye had the electrode placed on the cornea along the lower lid and the other eye had it positioned in the conjunctival sac. On a second day, the recordings were repeated with the alternative electrode placements. RESULTS: ERG, on-off and flicker responses were all smaller by between 20 and 25% when the DTL electrode was positioned in the conjunctival sac, compared to when it was positioned on the cornea, as did the scatter in the data points. This indicates that there is no advantage clinically for one or the other placement. CONCLUSIONS: Our results confirm other reports examining the effect of electrode position on electrophysiological potentials. When recording with the DTL electrode, it is important to ensure that it is placed at the same position in repeat recordings or in multicentre trials and that it is stable and does not move during recording.

Transfer characteristics of subretinal visual implants: corneally recorded implant responses.

PURPOSE: The subretinal Alpha IMS visual implant is a CE-approved medical device for restoration of visual functions in blind patients with end-stage outer retina degeneration. We present a method to test the function of the implant objectively in vivo using standard electroretinographic equipment and to assess the devices' parameter range for an optimal perception. METHODS: Subretinal implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) consists of 1500 photodiode-amplifier-electrode units and is implanted surgically into the subretinal space in blind retinitis pigmentosa patients. The voltages that regulate the amplifiers' sensitivity (V gl) and gain (V bias), related to the perception of contrast and brightness, respectively, are adjusted manually on a handheld power supply device. Corneally recorded implant responses (CRIR) to full-field illumination with long duration flashes in various implant settings for brightness gain (V bias) and amplifiers' sensitivity (V gl) are measured using electroretinographic setup with a Ganzfeld bowl in a protocol of increasing stimulus luminances up to 1000 cd/m2. RESULTS: CRIRs are a meaningful tool for assessing the transfer characteristic curves of the electronic implant in vivo monitoring the implants' voltage output as a function of log luminance in a sigmoidal shape. Changing the amplifiers' sensitivity (V gl) shifts the curve left or right along the log luminance axis. Adjustment of the gain (V bias) changes the maximal output. Contrast perception is only possible within the luminance range of the increasing slope of the function. CONCLUSIONS: The technical function of subretinal visual implants can be measured objectively using a standard electroretinographic setup. CRIRs help the patient to optimise the perception by adjusting the gain and luminance range of the device and are a useful tool for clinicians to objectively assess the function of subretinal visual implants in vivo.

Prostaglandin E2 in the lung lavage fluid of premature newborns before and after surgical or medical closure of a patent ductus arteriosus.

To analyze the role of prostaglandin E2 in maintaining ductal patency in premature newborns, we measured the PGE2 concentration in the lung lavage fluid of nine patients within 24 h before and 4-8 h after surgical ligation of a patent ductus arteriosus and in two patients before and after closure of the ductus following intravenous indomethacin. The concentration of PGE2 ranged from 240 to 3770 pg/ml (mean 1666 +/- 1256 pg/ml) before operative intervention and show a significant decrease to 0-300 pg/ml (mean 93 +/- 106 pg/ml, P less than 0.001, Student's two-tailed t-test) within a few hours after ligation of the ductus arteriosus. The same significant decrease could be seen in two patients with successful indomethacin therapy (0.25 mg/kg in three doses/day) with concomitant ductus closure. In contrast, when indomethacin was given in a reduced dose (0.1 mg/kg in three doses/day), only a slight effect on PGE2 synthesis could be seen without closure of ductus arteriosus. We suggest that the fall of PGE2 levels in lung lavage fluid reflects the local synthesis in the ductus arteriosus itself and is responsible for the decrease induced by surgical ligation or pharmacological inhibition by indomethacin.

Leukotriene B4 is involved in hemodialysis-associated neutropenia.

Biosynthesis of leukotriene B4 (LTB4) was studied in ten patients with end-stage renal failure undergoing chronic hemodialysis with a cuprophane membrane. As compared to healthy subjects the low basal plasma levels of LTB4 quantified by radioimmunoassay after extraction and purification by HPLC showed no significant difference. The time-course of LTB4 release after contact of the blood with the dialysis membrane without further in vitro stimulation was characterized by a rapid increase by about 500% within the first 10 min, appearing approximately at the same time as the known fall of white blood cell count which reaches its nadir after 20 min. Analysis of further release showed a decline of LTB4 biosynthesis to basal levels at the end of hemodialysis. These results indicate that activation of the 5-lipoxygenase pathway is involved in hemodialysis-associated leukopenia and may contribute to the alterations in neutrophils of patients with chronic dialysis therapy.

Differences in arachidonic acid release, metabolism and leukotriene B4 synthesis in human polymorphonuclear leukocytes activated by different stimuli.

Products of the 5-lipoxygenase pathway were analyzed after different stimuli in human polymorphonuclear leukocytes prelabeled with 3H-arachidonic acid. Upon stimulation with the Ca2+ ionophore, A23187, polymorphonuclear leukocytes generate 118.2 +/- 18 pg [3H]dihydroxyeicosatetraenoic acids (diHETEs, including 3H-leukotriene B4 and its 6-trans-stereoisomers), after exposure to serum coated zymosan (35.8 +/- 9 pg) and N-fMet-Leu-Phe (39.5 +/- 9 pg). Conversion of 3H-arachidonic acid paralleled its release after A23187 and fMet-Leu-Phe exposure leaving only 13.8 +/- 7% and 13.6 +/- 3% of the released 3H-arachidonic acid unmetabolized, respectively. In contrast, after stimulation with serum-coated zymosan only a small fraction of the released 3H-arachidonate was converted to 5-lipoxygenase products leaving 73.0 +/- 5% of the released 3H-arachidonic acid unmetabolized. In parallel, leukotriene B4 synthesis was studied in unlabeled polymorphonuclear leukocytes, resulting in 40 +/- 15 ng upon A23187 stimulation, 4 +/- 0.9 ng upon stimulation with fMet-Leu-Phe and 1.8 +/- 0.9 ng after serum-coated zymosan, showing a different ratio of leukotriene B4 to 3H-diHETE for A23187 in contrast to serum-coated zymosan and fMet-Leu-Phe. These results indicate that the coupling between the release of the precursor fatty acid and the metabolism via the 5-lipoxygenase pathway differs greatly between different stimuli.

Increased leukotriene B4 synthesis in patients with primary hyperparathyroidism is normalized after parathyroidectomy: a study comparing parathyroidectomy to thyroid adenomectomy.

Synthesis of leukotriene B4 (LTB4) upon stimulation of peripheral blood samples with the calcium ionophore A 23187 was studied in patients with primary hyperparathyroidism who underwent parathyroidectomy. Preoperatively, an increased LTB4 concentration of 1.76 +/- 0.19 ng/ml plasma was found, vs. 0.95 +/- 0.28 ng/ml in healthy individuals. On the fourth day after operation, the LTB4 concentration was almost normalized, reaching 1.25 +/- 0.23 ng/ml plasma. At the same time, mean serum calcium levels were reduced from 6.1 +/- 0.6 meq/liter before operation to 4.53 +/- 0.28 meq/liter after operation. In a control group, euthyroid patients with thyroid adenomas who underwent adenomectomy had normal LTB4 levels before operation (0.84 +/- 0.11 ng/ml) and did not show significant changes in LTB4-synthesizing capacity. The results indicate that synthesis of LTB4 in vivo may depend in part on factors related to serum calcium concentration or calcium metabolism.

Inhibition of leukotriene B4 formation in human neutrophils after oral nafazatrom (Bay g 6575).

Three grams of nafazatrom (Bay g 6575), given orally to healthy male volunteers in a single dose, significantly reduce the formation of leukotriene B4 in polymorphonuclear leukocytes. LTB4 synthesis fell from 57.1 +/- 17.0 ng/10(7) PMNL, mean +/- S.D., in control to 34.3 +/- 14.4 ng/10(7) PMNL 3 hr after nafazatrom (2 P less than 0.001). In vitro, nafazatrom inhibited LTB4 formation in human PMNL in a dose dependent manner. At 1 microM nafazatrom LTB4 formation was reduced to 65% of the control value. Nafazatrom had no effect on the excretion of 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, the major urinary metabolites of endogenously synthesized PGI2 and TXA2, respectively. Serum levels of TXB2 in clotted whole blood also remained unchanged. The inhibitory effect of nafazatrom on leukotriene biosynthesis in human PMNL suggests a therapeutic potential of this drug in processes like allergy and chronic inflammation, where leukotrienes play a pathogenetic role.

Anti-asthmatic effects of onions. Alk(en)ylsulfinothioic acid alk(en)yl-esters inhibit histamine release, leukotriene and thromboxane biosynthesis in vitro and counteract PAF and allergen-induced bronchial obstruction in vivo.

Five alk(en)ylsulfinothioic acid alk(en)yl-esters isolated from onions and four synthetic thiosulfinates inhibited 5-lipoxygenase of porcine leucocytes, histamine release and leukotriene B4 and C4 biosynthesis of human polymorphonuclear leucocytes, thromboxane B2 biosynthesis by human platelets and allergen- and PAF-induced bronchial obstruction of guinea-pigs. The anti-asthmatic and anti-inflammatory effects of onions depend in part on the thiosulfinate moiety: (Formula: see text).

Nonlinear pulse reflections from chirped fiber gratings.

We study the nonlinear evolution of optical pulses reflected from a chirped fiber grating experimentally and with numerical simulations. Over a broad range of grating parameters the nonlinearly reflected pulse splits into a pair of pulses in the range of incident pulse intensities where the transmitted pulse is a single narrowed pulse evolving into a fundamental soliton.

Personality disorder diagnoses in patients with bulimia nervosa: clinical correlates and changes with treatment.

BACKGROUND: In view of reports of a high incidence of Axis II disorders among patients with bulimia nervosa, we assessed personality diagnoses and traits in a sample of bulimic patients both preceding and following treatment for the eating disorder. METHOD: The Personality Disorder Examination, a structured interview to assess DSM-III-R personality disorders, was administered to 34 in-patients and 49 outpatients with bulimia nervosa entering treatment. Thirty of 49 outpatients were reassessed after 6 weeks of treatment with desipramine or placebo. RESULTS: At initial assessment, 38% of inpatients (N = 13) and 29% of outpatients (N = 14) fulfilled criteria for at least one personality disorder, most frequently borderline personality disorder. There were significant correlations between Personality Disorder Examination trait scores and clinical measures of eating disorder and depressive symptoms. Of 30 outpatients who were reinterviewed following treatment, 3 of 9 patients lost one or more personality diagnoses at post-treatment assessment, and 2 of 21 patients without initial Personality Disorder Examination diagnoses received one or more diagnoses at the second interview. Changes in Personality Disorder Examination trait scores, but not diagnoses, were correlated with changes in some clinical measures. CONCLUSION: These data suggest that the assessment of Axis II disorders in patients with bulimia nervosa is problematic and raise the possibility that personality features in this group may be influenced by the course of their Axis I disorder.

Hypertension: the East European experience.

Some differences (and similarities) between Eastern Europe and the rest of the Continent are presented regarding the treatment of hypertension. Based on data from the WHO Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) study, the prevalence of hypertension, and the proportion of uncontrolled hypertension, is clearly higher in Eastern Europe. According to one local long-term observer, a trend for further increases in prevalence is discernable. Comparative drug consumption studies are desirable. Regarding national experiences with hypertension and health care in general, there are also some important sociocultural differences; anecdotal observations are reported that support this assertion.

Alteration of monocyte function following major injury.

The macrophage exerts its stimulatory and regulatory functions within the specific immune response via the interleukin 1 (IL-1) and prostaglandin E2 (PGE2), respectively. In a screening study of macrophage-related variables following injury, a total of 58 patients (mean age, 32 years; mean injury Severity Score, 38), macrophagic phenotyping with the monoclonal antibody Leu M3 and serial measuring of the antagonistic monokines IL-1 and PGE2 and of the macrophage-activating lymphokine interferon gamma were carried out on posttrauma days 0, 1, 3, 5, 7, 10, 14, and 21. The posttraumatic course was characterized by significant monocytosis, showing a peak value of 32% of Leu M3-positive cells compared with 15% of these cells in normal control subjects. During the posttrauma course, the macrophagic PGE2 output was significantly elevated up to eightfold on days 5 and 7 compared with that of control subjects (0.441 +/- 0.14 ng/mL vs 0.052 +/- 0.01 ng/mL). Conversely, macrophagic IL-1 synthesis was significantly suppressed until day 10. Levels of interferon gamma were suppressed to a significant degree during the two-day observation period, with a trend to slow recovery at the end of week 3. These data suggest that a negative regulatory macrophagic function may be the event initiating posttraumatic immunosuppression. To restore impaired macrophagic T-helper cell interaction, cyclo-oxygenase inhibition and substitution of interferon gamma may be useful to potentiate facilitatory macrophagic function and to block inhibitory macrophagic activity.

Equal blood pressure levels carry different risks in different risk factor combinations.

It is well known that combinations of risk factors result in higher risk than their mere sum. The present paper describes, in quantitative terms, the differences between risks pertaining to equal blood pressure elevations at different constellations with other risk factors (smoking and hypercholesterolaemia). From the practical point of view, this concept of 'constellation risk' convincingly underscores the need for controlling, in hypertensive patients, coexisting hypercholesterolaemia and smoking. Also, at equal blood pressure elevations, smoking and hypercholesterolaemic patients are in greater need of antihypertensive medication. This applies in particular to the range of mild hypertension, where individual decisions have to be taken whether to initiate drug treatment.

Assessing the quality and effects of hypertension control in populations.

The objectives of hypertension control include early detection, treatment and prevention of blood pressure (BP) elevations. In clinical situations, continuous evaluation of an Individual's treatment is an inherent part of normal follow-up. On the level of populations, however, evaluation of hypertension control calls for specially designed action. Evaluation is needed for several reasons; these are, inter alia, strategic (to improve the method); economic (to upgrade cost-effectiveness); and ethical reasons (to morally justify public action). Since hypertension control in populations is itself a complex process, its evaluation requires, multidimensional approaches. The methodologic experience from three WHO studies of this kind has been reported. These were done in different contexts: (1) evaluation of the effects of a special multicentre programme for hypertension control in populations; (2) long-term monitoring of cardiovascular disease incidence; and (3) a project for the assessment of levels and quality of hypertension control that is taking place spontaneously. In the first study, changes with time were compared in pairs of similar communities, of which one had been exposed to an organized programme for the control of hypertension ('intervention' vs 'reference' community). The second study uses an elaborate system of disease registers and surveys periodically a number of general populations. In the third study the actual level and quality of hypertension control was analysed in different, mostly European, populations; the findings related to the treatment of hypertension were compared with the standards suggested by WHO and ISH; other findings were assessed on the basis of common sense.

Auditing hypertension control and management: a position paper.

The categorical term "auditing" hypertension control is chosen on purpose, to emphasize the responsibility of health politicians for assessing the quality and effects of interventions in populations. Auditing of hypertension is needed for reasons of Efficacy, Economics and Ethics. An analysis of efficacy should test whether the local strategies of hypertension control are sufficiently adapted to the needs and characteristics of a given population. Economic analyses should consider hypertension control in the perspective of resources and priorities. The ethical imperative requires an assessment and follow-up of the effects of health measures on the population, by the same token as evaluation of treatment results is obligatory in clinical medicine. The WHO/WHL Hypertension Management Audit Project was an attempt to analyze the repercussions of hypertension control programs on selected population. Five approaches were taken: (i) assessment of the epidemiological situation; (ii) clinical analysis on a sample of patients; (iii) assessment of patient satisfaction and of (iv) physicians' knowledge and attitudes; and (v) drug utilization studies. The results showed (a) a mixture of under- and overdiagnosis of hypertension in populations; (b) undertreatment of various degrees; (c) mixed patient satisfaction; (d) partial compliance of physicians' concepts and attitudes with standards promulgated by WHO and ISH; and, (e) great differences (at the time of the study) between drug utilization patterns in different countries.

WHO-WHL Hypertension Management Audit Project.

The quality of the control of hypertension has been assessed in 18 European population groups, in a multicentre cooperative project. Five approaches were taken: epidemiological survey, clinical evaluation of samples of patient records, assessment of patient satisfaction, exploration of physicians' attitudes and knowledge, and drug utilisation studies. The participating centres could choose any or all of the above approaches; a total of 31 subprojects was carried out. Undiagnosed hypertension varied in different centres from 17% to 34% of all hypertension, and not more than 29% of all treated hypertensive patients had attained normal BP. Diuretics were the most commonly prescribed drugs, followed by beta-blockers. Although physicians expressed their concern about other cardiovascular risk factors and declared that they considered nonpharmacological treatment important, the findings in the patient survey did not confirm such attitudes. Finally, an analysis of patient satisfaction showed a mixed pattern. In conclusion, the control of hypertension in populations, through detection and treatment, as well as patient education and physician information, was studied.

"Normal" control subjects are hard to find: a model for centralized recruitment.

A central program for recruiting "normal" control subjects is examined by considering the yield of subjects who meet criteria for "healthy" as defined by their personal and family histories of mental disorders. Of the 267 applicants, 30.3% have no lifetime diagnoses, 41.2% are currently healthy with a history of mental illness, and 27.7% are currently mentally ill. Only 16.1% met Research Diagnostic Criteria for "never mentally ill" and reported no family history of mental disorders. Benefits of a central recruitment program for studies of mental disorders include increased information on a large subject pool and decreased volunteer bias.

The impact of prior substance abuse on treatment outcome for bulimia nervosa.

The present investigation examined the significance of a past history of substance abuse on treatment outcome for bulimia nervosa. Seventy-five women with bulimia nervosa participated in a 6-week double-blind outpatient trial of desipramine; 19 patients had a history of substance abuse and 56 did not. Although patients with a history of substance abuse reported higher levels of anxiety and depression at presentation for treatment than patients without such histories, the two groups reported a similar age of onset of their bulimia nervosa and similar severity of eating pathology with regards to binge and vomit frequencies and measures of concern about body shape and weight. On all outcome measures, the improvement of the substance abuse group was equal to or greater than that in the group without a history of substance abuse. Results suggest that a past history of substance abuse has no implication regarding response to pharmacological treatment for bulimia nervosa.

Cost-effective control of rheumatic fever in the community.

Rheumatic fever is declining rapidly in importance in the developed countries, but is still a major public health problem in the developing countries. Primary prevention techniques, consisting of the detection and antibiotic treatment of streptococcal infections of the pharynx, are both feasible and effective, but are also costly, as only 10-20% of all pharyngeal infections are due to the beta-hemolytic Streptococcus, and only a small proportion of those actually develop into rheumatic heart disease. A different concerted approach, which is both effective and economically entirely justifiable, is to use antibiotics as a prophylaxis to prevent secondary infection, i.e. relapses of rheumatic fever. A multi-centre study conducted by the WHO has shown that the cost of antibiotics used for secondary prevention was less than the savings resulting from the lower incidence and shorter hospital stays of recurrencies of rheumatic fever. Given economic restrictions, therefore, priority is given to organized and systematic secondary prevention.

[Use of the risk factor concept in cardiovascular diseases (author's transl)]. / Utilisation du concept de facteur de risque en pathologie cardiovasculaire

The essential implication of the notion of risk factor is that preventive action should be undertaken if certain factors, predisposing to cardiovascular diseases are present in an individual or in a group. Risk factors are thus categorized from the pragmatic point of view, according to the relative ease and practicability of prophylactic intervention -- and their justification. A brief review of the risk factors of the major cardiovascular diseases (coronary heart disease, hypertension, chronic pulmonary heart disease, stroke, rheumatic heart disease and congenital malformations) shows that the risk factor concept is the basis of preventive cardiology.