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Biomedical subjects

L Eriksson

Publications and source records attributed to L Eriksson.

At least 55 records · Page 3Linked to original sources
PubMed1998

New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids.

In this study 87 amino acids (AA.s) have been characterized by 26 physicochemical descriptor variables. These descriptor variables include experimentally determined retention values in seven thin-layer chromatography (TLC) systems, three nuclear magnetic resonance (NMR) shift variables, and 16 calculated variables, namely six semiempirical molecular orbital indices, total, polar, and nonpolar surface area, van der Waals volume of the side chain, log P, molecular weight, and four indicator variables describing hydrogen bond donor and acceptor properties, and side chain charge. In the present study, the data from a previous characterization of 55 AA.s from our laboratory have been extended with data for 32 additional AA.s and 14 new descriptor variables. The new 32 AA.s were selected to represent both intermediate and more extreme physicochemical properties, compared to the 20 coded AA.s. The new extended and updated principal property scales, the z-scales, were calculated and aligned to previously reported z(old)-scales. The appropriateness of the extended z-scales were validated by the use in quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues and in a QSAM of 29 neurotensin analogues.

Amino Acids↗
PubMed1998

Cerebral effects of nicotine during cognition in smokers and non-smokers.

For the smoker, nicotine has a positive effect on attention, cognition and mood. Conversely, nicotine abstinence is characterized by uncomfortable psychological effects such as impaired attention, but also irritability. We postulated that nicotine exerts an effect on cerebral areas important for attention and mood. Regional cerebral blood flow (rCBF), as an index for cerebral activity, was measured in both smokers and non-smokers. They were scanned during performance of a psychometric task with and without i.v. infusion of nicotine (1-methyl-2-[3-pyridyll] pyrrolidine). Nicotine induced rCBF decreases in the anterior cingulate cortex and the cerebellum, and concomitant increases in the occipital cortex. The changes were similar in nature and magnitude in smokers and non-smokers. Thus, specific changes were induced in areas pertaining to the anterior attention system and to higher order visual cortex. We conclude that these effects on cerebral activity provide insights into the desired positive effects of nicotine on cognition as well as the negative effects experienced during nicotine abstinence.

Adult↗
PubMed1998

Pharmacokinetics of meropenem in patients with cystic fibrosis.

The pharmacokinetics of meropenem were studied after single i.v. infusions of 15 mg meropenem/kg body weight in eight subjects with cystic fibrosis (CF) and eight healthy volunteers matched for age, sex, and weight. Significantly shorter terminal half-lives (mean, 0.74 h vs. 0.99 h) and mean residence times (mean, 1.09 h vs. 1.39 h) were noted in CF subjects. Plasma and renal clearances tended to be higher and distribution volumes smaller among the patients, but differences were not statistically significant. The results are consistent with the findings for many other beta-lactam agents used in CF patients. Assuming a MIC90 of 4 mg/l for meropenem against Pseudomonas aeruginosa, the time above the MIC was less than 3.3 h in six of the eight CF patients. This finding should be kept in mind when designing treatment regimens with meropenem in CF subjects.

Adult↗
PubMed1998

XY sex reversal in the wood lemming is associated with deletion of Xp21-23 as revealed by chromosome microdissection and fluorescence in situ hybridization.

In the wood lemming (Myopus schisticolor), XY sex reversal occurs naturally because of the presence of an X chromosome variant designated X*. The two types of X chromosome, X and X*, can be distinguished by G-banding, and analyses have demonstrated complex rearrangements of the short arm of X*. Here, chromosomal microdissection, degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and fluorescence in situ hybridization (FISH) techniques have been used to generate and map DNA probes for different parts of the X and X* chromosomes. The results showed that the region of Xp21-23 is deleted from the X* and some of the deleted DNA sequences are homologous to the mouse gamma-satellite. The deletion must be associated with the sex reversal in this species. FISH experiments with dissected probes of X and distal half of Xq provided evidence for presence of homologous sequences between large regions of the X and Y chromosomes, including euchromatic and heterochromatic parts of the sex chromosomes. The findings of this study will be of significance for further cloning of important candidate gene(s) responsible for the XY sex reversal.

Animals↗
PubMed1998

Lung transplantation at the University of Lund 1990-1995. Analysis of the first 39 consecutive patients.

Between 1990 and 1995 39 patients were lung transplanted at the University Hospital in Lund. This is a retrospective review of survival and lung function in these patients. There were 17 single-lung transplants (SLT), 21 double-lung transplants (DLT) and 1 heart-lung transplant (HLT). Seven patients died during the period, giving an overall survival of 82%. One-year survival according to Kaplan-Meier survival analysis was 87%, and 2-year survival was 83%. Vital capacity and forced expiratory volume in 1 s (FEV1) 1 year after transplantation were 91% and 100% of predicted, respectively, in the DLT group and 60% and 50% in the SLT group. Bronchiolitis obliterans syndrome (BOS) developed in 11 of the 35 patients (31%) surviving more than 6 months, 2/21 in the DLT group and 8/13 in the SLT group and in the patient with HLT. The median time until detection of BOS was 11 months after the operation (range 6-18 months). Working capacity 1 year after transplantation was 60% of predicted in the DLT group and 47% of predicted in the SLT group. Ventilatory capacity was no longer function limiting. Lung transplantation today is a therapeutic option with a good medium-term survival and good functional results in selected patients with severe lung disease.

Adolescent↗
PubMed1998

Lung hyaluronan and water content in preterm and term rabbit pups exposed to oxygen or air.

Rabbit pups were delivered by cesarean section 1 or 2 d before term, or vaginally around term, and then reared in room air or exposed to intermittent or continuous hyperoxia (> 85%) for up to 9 d. Pups were killed at different ages, and lung hyaluronan (HA; microgram/g of dry lung weight) and lung water content, measured as wet/dry lung weight, were determined. Compared with the day of birth, the lung HA concentration did not change significantly on succeeding days in pups kept in air delivered 2 d (-2 d) or 1 d (-1 d) before term, whereas the water content decreased significantly. Continuous exposure to hyperoxia resulted in a significantly raised lung HA concentration 6 d postterm in both -2 d and -1 d pups, and intermittent exposure to hyperoxia resulted in a significantly raised HA concentration 6 d postterm in -1 d pups, compared with the groups exposed to room air. These increases were accompanied by significantly elevated wet/dry lung weight ratios. Microscopic examination revealed significantly increased HA staining scores in alveoli, arterioles, and bronchioli in both hyperoxia-exposed groups of -2 d pups 6 d postterm, and nonsignificantly higher scores in -1 d and vaginally delivered pups of comparable age, compared with the scores at birth. The results indicate that oxygen exposure neonatally may result in an increase in lung HA accompanied by an increase in lung water content. The increase in lung HA concentration in our study may be an effect of oxygen free radicals or of oxygen-induced stimulation of inflammatory mediators.

Air↗
PubMed1998

Developmental gene expression of sympathetic nervous system tumors reflects their histogenesis.

Comparisons of the developing human sympathetic nervous system (SNS) to tumors presumed to derive from these cells may suggest tumor progenitors and predict tumor biologic behavior. Classic neuroblastoma (NB) and its more highly differentiated stroma-rich subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma were examined for the presence of the developmentally characterized gene products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine hydroxylase. The marker gene expression profiles of these tumors were compared with those similarly determined for a number of normal prenatal and postnatal human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich NB display marker expression profiles mimicking those of childhood sympathetic paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively. A selection of differentiating, extra-adrenal NB tumors with prognostically favorable features possess marker gene expression profiles paralleling that observed for fetal extra-adrenal sympathetic paraganglia/small intensely fluorescent cells. In contrast, undifferentiated, clinically aggressive NB tumors manifest characteristics mirroring that of embryonic/early fetal sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland. These findings suggest that clinical features, such as primary tumor location and age at diagnosis, provide prognostic information for NB patients by virtue of the existence and biology of the presumed tumor progenitor cell type.

Adrenal Gland Neoplasms↗
PubMed1998

Improved blood preservation with 0.5CPD erythro-sol. Coagulation factor VIII activity and erythrocyte quality after delayed separation of blood.

BACKGROUND AND OBJECTIVES: Delay between blood collection and the separation of its components may result in lowered yield of factor VIII (FVIII) and loss of 2,3-biphosphoglycerate (2,3-BPG). This study was to see whether the use of 0.5 CPD resulted in better preservation of FVIII and maintenance of 2,3-BPG. MATERIALS AND METHODS: 55 units of blood were collected in 0.5CPD and 48 in CPD SAG-M. Ten of the collections were paired, so that the same donors were bled in a single session partly in an 0.5CPD system and partly in CPD SAG-M. After collection, the blood was promptly cooled to 20 degrees C and stored at that temperature for up to 24 h. RESULTS: Preservation of FVIII activity was significantly better in 0.5CPD compared with CPD. The content of von Willebrand factor was stable in the anticoagulant solutions for 24 h at that temperature. Plasma separated from both media had how levels of prothrombin fragment 1 + 2 and complement activation. Paired collections substantiated previous reports that red cell storage is significantly improved in 0.5CPD compared with CPD SAG-M with respect to 2,3-BPG and haemolysis. CONCLUSIONS: Red cell metabolism and oxygen-releasing capacity are kept at acceptable levels in 0.5CPD blood for 24 h at 20 degrees C before component separation. The concentration of red cell 2,3-BPG remained at normal or slightly subnormal levels during further storage in 0.5CPD at 4 degrees C for 2-4 weeks before gradual decay to an average of 39% at 48 days.

2,3-Diphosphoglycerate↗
PubMed1998

Diurnal rhythm of melatonin in bovine milk: pharmacokinetics of exogenous melatonin in lactating cows and goats.

We investigated whether the melatonin levels in bovine milk exhibit a similar daily rhythm as serum levels. In 4 Ayrshire cows at the beginning of the lactation period in May the nocturnal rise in milk melatonin was moderate (from 7 +/- 2 pg/ml at noon to 15 +/- 1 pg/ml at night; mean +/- SEM) and did not correlate well with the melatonin level in serum (from 7 +/- 2 pg/ml to 27 +/- 7 pg/ml, respectively). On the other hand, 6 cows in a later phase of lactation, studied in February, showed a clear long-lasting nocturnal melatonin increase both in serum (from 9 +/- 1 pg/ml at noon to 26 +/- 3 pg/ml at night) and in milk (from 12 +/- 5 pg/ml to 26 +/- 7 pg/ml, respectively). Melatonin kinetics during lactation was studied in more detail in 4 Ayrshire cows and 4 dairy goats by giving an intravenous bolus injection of melatonin. A 3-compartment model with melatonin elimination from the central compartment was used to describe the data. The values (mean +/- SD) for the cows and the goats were: elimination half-life 27 +/- 4 min and 27 +/- 1 min, mean residence time 24 +/- 4 min and 18 +/- 4 min, steady state distribution volume 1.0 +/- 0.3 l/kg and 0.6 +/- 0.1 1/kg (p < 0.05), and plasma clearance 0.044 +/- 0.004 l/kg/min and 0.035 +/- 0.011 l/kg/min, respectively. Following injection, the melatonin concentration in milk increased rapidly and exceeded the corresponding serum value 15-30 min later, remaining thereafter above the serum level. Our results suggest that milk melatonin levels reflect blood concentrations of melatonin with a short delay.

Animal Husbandry↗
PubMed1997

International forum: Europe. Buffy-coat-derived platelet concentrates: Swedish experience.

The need for source material for plasma products such as factor VIII preparations and improving the quality of red cells for transfusion became determining factors in the choice of methods for blood components in the 1970s and 1980s in Sweden. The possibility to make platelet concentrates (PC) from buffy coats (BC-PC) instead of from platelet-rich plasma (PRP-PC), as first described in England and The Netherlands, using an additive solution as the major component of the platelet storage medium, as first described by Rock et al., has been shown to influence favourably the national supply of blood components and has become accepted as the normal standard procedure in the first half of the 1990s. Leucocyte-depleted PCs, produced from pools of 4-6 BCs, used in all multiple platelet transfusions to thrombocytopenic patients, have strongly reduced the demand for HLA compatible PCs. Nationwide, 79% of the demand of PCs is supplied as BC-PCs, mostly leuco-depleted which, so far, have compared favourably with apheresis-PCs for cost-effectiveness.

Blood Component Removal↗
PubMed1997

In vivo biodistribution of [N-11C-methyl]KF 17837 using 3-D-PET: evaluation as a ligand for the study of adenosine A2A receptors.

(KF 17837, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine, was 11C-labelled by methylation at N-7 of the nor-compound, KF 17440, using [11C]methyl iodide. Radiochemical conversions of 50% or 70-80% were obtained using sodium hydride or potassium carbonate, respectively, as base. Total synthesis time was 40-45 min, including isolation by semipreparative liquid chromatography. Cerebral uptake of [N-11C-methyl]KF 17837 in Cynomolgus monkeys, evaluated using positron emission tomography (PET), was so low that regional differences in distribution kinetics were revealed first after increasing injected dose 3-fold and using 3-D mode of data acquisition. At all times, the relative regional retention (maximum striatum:cerebellum: cortex approximately 1.1:1:0.8 at 20 min) was considerably different from the known relative density of A2A receptors in these regions. Radioactivity decreased more rapidly in the cortex than in the striatum and cerebellum (by 20% vs. 3-7%, respectively, between 5 and 50 min). Addition of carrier to [N-11C-methyl]KF 17837 only marginally affected the cerebral radiotracer uptake. By contrast, in the heart the initial tracer uptake was high and the elimination kinetics was enhanced by adding unlabelled carrier. We have thus shown that KF 17837 passes the blood-brain barrier, though to a very low extent. This fact and the apparently high nonspecific binding in vivo of [N-11C-methyl]KF 17837 in regions with low receptor densities limits its usefulness as a ligand for quantification of the adenosine A2A receptors in the primate brain.

Animals↗
PubMed1997

N-methylquipazine: carbon-11 labelling of the 5-HT3 agonist and in vivo evaluation of its biodistribution using PET.

N-Methylquipazine (2-[1-(4-methyl)-piperazinyl)quinoline)) was labelled with carbon-11 by reacting [11C]methyl iodide with the nor-compound, quipazine. Radiochemical conversions were 79 +/- 7%, based on the alkylating agent. The total synthesis time including purification was 40 to 45 min. N-[Methyl-11C]methylquipazine thus synthesized was >99% radiochemically pure, and the specific activity ranged between 12-37 GBq/mumol. Dynamic imaging with PET was used to examine in vivo its distribution in rat and monkey. In rat the organ uptake at intermediate times was: liver > heart > whole brain > or = lung > extracerebral tissue. Brain uptake and wash-out were rapid: A maximum was reached in 2 to 3 min with subsequent decrease to approximately equal to 50% the peak value by 13 min. In monkey the tracer uptake was heterogeneous and high in regions known to contain 5-HT3 receptors but also in regions devoid of these receptors. Tissue kinetics were similar for all regions (initial rapid accumulation with tmax < or = 7 min, followed by slow decrease with all regions approaching the level of the cerebellum at 30 to 35 min). Pretreating with quipazine significantly decreased only the ratio of uptake in the medulla oblongata compared to the cerebellum. Although the nonspecificity of its binding limits the usefulness of N-[methyl-11C]methylquipazine, both its kinetic behavior and the blocking results indicate that a more selective arylpiperazine might prove to be a more attractive tracer for PET studies of 5-HT3 receptors.

Animals↗
PubMed1997

Storage of buffy coat preparations at 22 degrees C in plastic containers with different gas permeability.

BACKGROUND: Buffy coats (BCs) are used as an alternative to platelet-rich plasma in the preparation of platelet concentrates (PCs). For this purpose the BCs have to be stored for same time at 20-24 degrees C which implies cellular metabolic activity. However, little information is available concerning the effects of a number of factors which may influence the suitability of the preparation as the source of PC. STUDY DESIGN AND METHODS: We studied the effects on BCs of a high and low gas permeability of the wall of the plastic containers, PL2209 and PL146, respectively, mixing versus non-mixing during storage for 48 h at 22 degrees C, and two types of anticoagulant solutions, CPD and half strength citrate CPD (0.5CPD). The buffy coats were prepared by the bottom and top technique. The median values of volume and haematrocrit were 58-64 ml and 39-45%, respectively. A total of 48 BCs were tested. Blood gases, pH, bicarbonate concentration and haemolysis were determined in the blood mixtures and beta-thromboglobulin (beta-TG), lactate dehydrogenase (LDH), complement factor 3a, and elastase in the extracellular fluid. RESULTS: The pH decreased in all units but to a lesser extent in PL2209 containers than in PL146 units. In the former the pCO2 decreased slowly in contrast to the latter where it increased by about 50%. Mixing during storage increased the pH and decreased the pCO2 in 0.5CPD-PL146 and CPD-PL2209 units, as compared to resting, while no effects of mixing were observed in the other groups. The pO2 decreased to low levels in PL146 units. The haemolysis and LDH release were higher in mixed than in unmixed units. The initial beta-TG levels were lowest in 0.5CPD-PL146 units which also had the lowest 24-hour levels. The release of beta-TG during storage was smallest in CPD resting units. The elastase release was significantly higher in 0.5CPD than in CPD units already from the beginning of storage and increased during storage at about the same rate irrespective of mixing. The C3a levels were higher in 0.5CPD-PL2209 units than in the other units at 2 h. Storage for 24 h caused an increase by 2-3 times of the original level without any clear relation to storage conditions. CONCLUSIONS: In BC units accumulation of CO2 occurs in containers with low gas permeability. These also show the most rapid pH decrease during storage. Prolonged holding of BCs puts extra emphasis on the need of satisfactory gas permeability of the container for platelet storage in BC-derived PCs. Continuous mixing causes red cell damage and does not seem to have any clear benefit. The release of granulocyte elastase was higher in 0.5CPD than in CPD units but there was no indication of an associated increase in platelet activation. SUMMARY: Study of buffy coats stored in various media and containers at 22 degrees C suggests that it is better to restrict storage to 24 h or less to avoid activation or other deleterious effects on the platelets.

Blood Gas Analysis↗
PubMed1997

Clinical and laboratory experience with erythrocyte and platelet preparations from a 0.5CPD Erythro-Sol opti system.

BACKGROUND: Red blood cells stored as concentrates or suspensions in additive solutions change rapidly their oxygen affinity mainly due to the loss of 2,3-diphosphoglycerate (2,3-DPG). When collected in CPD with half of the normal concentration of citrate and citric acid (0.5CPD) and stored in a new additive solution (Erythro-Sol), 2,3-DPG is better maintained. No studies of the oxygen affinity of red cells stored under these conditions have been published. In Erythro-Sol, red cells have a satisfactory in vivo recovery for 49 days but the conditions after 28 days, within which time most red cell units are transfused, have not been investigated. Of importance is also to be able to make platelet concentrates (PCs) from 0.5CPD blood. Little data are available concerning the clinical usefulness of platelets prepared from 0.5CPD buffy coats (BCs). METHODS: Blood was collected in 0.5CPD, held at 20 degrees C for 3-4 h, then separated with the bottom-and-top technique into red cells, plasma and BC. In a storage experiment with 6 U the 2,3-DPG and P50 values were determined weekly and a number of in vitro parameters were tested on day 28. In 6 donors the in vivo recovery and survival of red cells were determined using a single-chromium technique. Transfusions of 212 0.5CPD-Erythro-Sol red cell units were given to hematological patients under supervision. PCs derived from pools of 0.5CPD BCs suspended in PAS2 (T-Sol) were transfused to 20 thrombocytopenic patients and compared with CPD-BC-PCs suspended in PASI. Corrected count increments (CCI) were determined. RESULTS: The erythrocyte 2,3-DPG and P50 values were normal or slightly subnormal initially but increased to supernormal levels during the 1 week, and remained at these levels for a further 1-3 weeks; the 2,3-DPG was two thirds of normal after 28 days, the P50 was 3.72 +/- 0.28 kPa after 14 days and 2.84 +/- 0.41 after 28 days (mean +/- SD). The P50 values corresponded closely (r2 = 0.903) to 2,3-DPG. The in vivo recovery of 4-week-stored red cells was 89.6 +/- 5.5% and the T50 was 32.2 +/- 2.0 days. No adverse effects were observed in the transfusions. The CCI values did not differ between test and control groups; in both, 3- to 5-day-stored PCs gave lower CCI than fresh (0-2 days) PCs. Patients with acute myeloid leukemia AML (n = 11) had significantly lower CCI values than patients with myelodysplastic syndrome, myeloma and lymphoma (n = 9; CCI 1 h: p = 0.001; CCI 24 h: p = 0.006). CONCLUSIONS: Red cells stored in Erythro-Sol sustain a normal or slightly lowered oxygen affinity for 2-4 weeks, their viability is excellent, and they are well tolerated in clinical transfusions. Platelets prepared from 0.5CPD-BCs cause CCI, of the same magnitude as CPD-BCs.

Anticoagulants↗
PubMed1997

Brief episodes of ventricular fibrillation do not influence postischemic cerebral perfusion assessed by positron emission tomography.

OBJECTIVES: To establish the defibrillation threshold in patients receiving an implantable cardioverter defibrillator, at least three episodes of ventricular fibrillation are induced and converted back to regular rhythm, using direct current countershocks. The aim of this study was to examine the influence of repeated short episodes of ventricular fibrillation on global and regional cerebral perfusion. DESIGN: A prospective, descriptive study. SETTING: A positron emission tomography laboratory at a university hospital. PATIENTS: Four patients, admitted for defibrillation threshold tests 2 yrs after the implantation of a cardioverter defibrillator, were included in the study. Global and regional cerebral blood flow was measured by cerebral positron emission tomography, using an 15O-labeled tracer under propofol-induced general anesthesia. Electroencephalograms (EEGs) were concomitantly recorded. INTERVENTIONS: Induction and conversion of ventricular fibrillation. MEASUREMENTS AND MAIN RESULTS: No effect on global cerebral perfusion was observed after induced ventricular fibrillation lasting 21 +/- 3 secs. The average global cerebral perfusion was 23 +/- 1 mL/100 g/min after induction of anesthesia and 31 +/- 8 mL/100 g/min and 24 +/- 2 mL/100 g/min immediately after the termination of the first and second ventricular fibrillation episodes, respectively. Ten minutes after the second and the third threshold tests, global cerebral perfusion was 21 +/- 1 mL/100 g/min and 21 +/- 2 mL/100 g/min, respectively. Regional cerebral perfusion and EEGs were not influenced. CONCLUSION: Short episodes of ventricular fibrillation did not induce any measurable effects on global and regional cerebral perfusion detectable by positron emission tomography 30 secs and 10 mins after restitution of sinus rhythm.

Aged↗
PubMed1997

Clinical safety of enamel matrix derivative (EMDOGAIN) in the treatment of periodontal defects.

The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.

Adult↗