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Biomedical subjects

L O Hansson

Publications and source records attributed to L O Hansson.

At least 37 records · Page 2Linked to original sources
PubMed1999

A glutamatergic deficiency model of schizophrenia.

Although the presence of hyperdopaminergia has been demonstrated in the brains of people with schizophrenia, at least in some circumstances, other neurotransmitters are important in this disorder, and a glutamatergic deficiency model of schizophrenia is proposed. It is suggested that the amount of sensory input allowed to reach the cerebral cortex is restricted by an inhibitory effect of the striatal complexes on the thalamus, thereby protecting it from being overwhelmed. Several strands of evidence are presented to support the concept that a weakened glutamatergic tone increases the risk of sensory overload and of exaggerated responses in the monoaminergic systems that could result in psychosis.

Biogenic Monoamines↗
PubMed1998

An evolutionary approach to the design of glutathione-linked enzymes.

Studies of protein structure provide information about principles of protein design that have come into play in natural evolution. This information can be exploited in the redesign of enzymes for novel functions. The glutathione-binding domain of glutathione transferases has similarities with structures in other glutathione-linked proteins, such as glutathione peroxidases and thioredoxin (glutaredoxin), suggesting divergent evolution from a common ancestral protein fold. In contrast, the binding site for glutathione in human glyoxalase I is located at the interface between the two identical subunits of the protein. Comparison with the homologous, but monomeric, yeast glyoxalase I suggests that new domains have originated through gene duplications, and that the oligomeric structure of the mammalian glyoxalase I has arisen by 'domain swapping'. Recombinant DNA techniques are being used for the redesign of glutathione-linked proteins in attempts to create binding proteins with novel functions and catalysts with tailored specificities. Enzymes with desired properties are selected from libraries of variant structures by use of phage display and functional assays.

Binding Sites↗
PubMed1998

Hydatidiform mole with non-metastatic pulmonary complications and a false low level of hCG.

We present a case of hydatidiform mole with non-metastatic pulmonary complications and stress that termination of the pregnancy will cure the patient. The frequent use of sonography in early pregnancy makes it possible to diagnose pathological pregnancies earlier than was possible before. The fact that molar pregnancies are now being terminated at an earlier stage means that some of the complications associated with advanced moles are seldom encountered today. The case also illustrates the so-called 'high dose hook effect' meaning that an extremely high level of hCG may falsely be reported to be very low by the laboratory.

Adult↗
PubMed1997

Mechanism-based phage display selection of active-site mutants of human glutathione transferase A1-1 catalyzing SNAr reactions.

A library of active-site mutants has been constructed by targeting selected amino acid residues in human glutathione transferase (GST) A1-1 for random mutagenesis. The mutated residues are suitably positioned for interaction with the second, electrophilic substrate, in particular chloronitrobenzene derivatives undergoing SNAr reactions. DNA representing the GST A1-1 mutant library was fused with DNA encoding gene III protein, a component of the coat of filamentous phage. Phage display was used for affinity selection of GST A1-1 mutants with altered catalytic properties. The affinity ligand used was the sigma-complex of 1,3,5-trinitrobenzene and glutathione immobilized to Sepharose. The complex was designed to mimic the transition state of SNAr reactions catalyzed by GSTs. The selection system is based on the combination of affinity for the sigma-complex as well as the ability to promote its formation, thus mimicking two salient features of the assumed catalytic mechanism for the SNAr reactions. Many of the GST A1-1 mutants selected and analyzed contained an aromatic amino acid residue in one of the mutated positions, suggesting favorable interactions with the trinitrocyclohexadienate moiety of the affinity ligand. A mutant C36 was selected for more detailed studies. Its catalytic efficiency with several chloronitrobenzene substrates was 20-90-fold lower than that of wild-type GST A1-1, but fully comparable to naturally evolved GSTs of different classes, providing a 10(5)-fold rate enhancement over the uncatalyzed reaction. In the conjugation of ethacrynic acid, a Michael addition reaction, mutant C36 was 13-fold more efficient than the wild-type enzyme. Within experimental error, the quotient between the KF values for wild-type GST A1-1 and mutant C36 is the same as that between the kcat/KM values determined with 1-chloro-2,4-dinitrobenzene for the two enzyme forms. This result indicates that sigma-complex formation is rate-limiting for the catalyzed reaction. Thus, the principle of transition-state stabilization as a component of catalysis has been successfully exploited in affinity selection of catalytically competent GST A1-1 mutants. This mechanism-based procedure also selects for the ability to promote sigma-complex formation, and serves as a probe of the catalytic mechanism.

Bacteriophages↗
PubMed1997

Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic implications.

The dopamine hypothesis has dominated schizophrenia research for decades but is now yielding to a more diversified view, where the interaction of several neurotransmitters in complex circuitries is under scrutiny. Especially, glutamatergic and serotonergic mechanisms are attracting attention. However, the role of dopamine also needs further exploration and may still turn out to have novel therapeutic applications. In the present minireview an attempt is made to integrate preclinical and clinical data on neurotransmitter aberrations in schizophrenia and to discuss their therapeutic implications.

Animals↗
PubMed1997

Sequential changes of inflammatory and nutritional markers in patients with community-acquired pneumonia.

The aim of the present study was to describe the long-term sequential changes of the acute phase proteins and of commonly used so-called nutritional markers in patients with community-acquired pneumonia (CAP), and to calculate the normalization rate of serum C-reactive protein (CRP), defined as the time for a 50% decrease, during the initial treatment of these patients. The long-term sequential changes of inflammatory and nutritional markers in patients with CAP have not been previously well-documented. However, in the diagnostic work-up of patients with suspected infectious diseases CRP levels are often used nowadays. Serum albumin, transthyretin (prealbumin), and transferrin together with serum iron, have often been used as "nutritional markers" in patients. We therefore studied the long-term changes of these parameters in patients with CAP, as these markers also are influenced by inflammatory reactions, in pneumonia for example. All the patients within the age range 50-85 years, with the exception of immunocompromised patients, who were admitted with CAP to the Department of Infectious Diseases at Danderyd Hospital during a 12-month period (January 1992-January 1993), were reviewed for inclusion in a prospective study of the long-term sequential changes of inflammatory and nutritional markers in CAP patients. A total of 97 patients (50 men) with a mean age of 69.6 years were included in the study. Blood samples were drawn on admission, during the hospitalization period, and at the follow-up visits. Serum CRP, alpha 1-antitrypsin, haptoglobin and orosomucoid (alpha 1-acid glycoprotein) were used as acute phase proteins. However, albumin, transthyretin, and transferrin together with serum iron and percentage transferrin saturation were also included. Of all the parameters studied, CRP showed the greatest variation, already having the highest values at admission. CRP also showed, together with iron, the earliest response to recovery in the patients. The median time for a 50% decrease of CRP was 3.3 days for the patients (n = 73) with more than two CRP values measured during the first nine days. Transthyretin responded faster to patient recovery than did albumin. CRP showed the greatest amplitude of changes and together with iron and percentage saturation of transferrin it also showed the earliest response to recovery in patients with CAP. This indicates that CRP is the best of the parameters studied for use in diagnostic work-up and in follow up.

Aged↗
PubMed1997

S100B protein, 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid as biochemical markers for survival prognosis in patients with malignant melanoma.

Elevated levels of the phaeomelanin metabolite 5-S-cysteinyldopa and the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid in urine and serum have been shown in previous studies to correlate with disseminated malignant melanoma. Immunohistochemical detection of S100B protein is an acknowledged method for the diagnosis of malignant melanoma, and it has been suggested that rising serum levels of S100B protein are associated with the survival rate of patients with malignant melanoma. In the present study serum levels of S100B protein and urinary concentrations of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid were measured in 91 patients with histopathologically verified malignant melanoma. At the time of sampling 13 patients were in clinical stage I, 13 in stage II and 65 in stage III. The urinary levels of the melanin metabolites were determined by automated high performance liquid chromatography, and the serum levels of S100B protein by an immunoradiometric assay with two monoclonal antibodies. The overall survival rate was most strongly associated with the serum levels of S100B protein (P < 0.001), but there was also a significant correlation to urinary levels of 5-S-cysteinyldopa (P < 0.001). A corresponding association with urinary levels of 6-hydroxy-5-methoxyindole-2-carboxylic acid was found in only a very few patients with extremely high urinary concentrations. A statistically significant increase in relative hazard was found for S100B protein levels exceeding 0.6 microgram/l (P < 0.001), and predictably for patients in clinical stage III (P < 0.001). An analysis of S100B protein levels in patients in clinical stage III showed a significant correlation to survival (P = 0.005). Our study suggests that of the three biochemical tumour markers, S100B and to a lesser extent 5-S-cysteinyldopa have the greatest potential to be used as predictors of survival prognosis in patients with malignant melanoma.

Adult↗
PubMed1996

Concurrent locomotor stimulation and decrease in dopamine release in rats and mice after treatment with the competitive NMDA receptor antagonists D-CPPene and CGS 19755.

The present study was aimed at investigating the effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonists D-CPPene (3-(2-carboxypiperazine-4-yl)-propenyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl)piperidine-2-carboxylic acid) on dopamine (DA) transmission and motor activity in mice and rats. As measures of DA release we used mouse brain 3-methoxytyramine (3-MT) levels, and indirect estimate of DA release, and striatal dialysate measures of DA in conscious and freely moving rats by means of microdialysis. To obtain additional information about monoaminergic neurotransmission, brain tissue levels of DA, DOPAC, HVA, 5-HT and 5-HIAA were measured in both mice and rats. The animals were sacrificed at the time when NMDA antagonist-induced locomotor stimulation was maximal. In mice, D-CPPene and CGS 19755 decreased striatal 3-MT levels, whereas, in general, 3-MT levels in the limbic forebrain were not significantly altered. Treatment with CGS 19755 decreased rat striatal dialysate levels of DA but increased 5-HIAA at time points when locomotor activity was increased. D-CPPene and CGS 19755 have been observed to produce psychotic symptoms in man. The present study suggests that these symptoms are not a result of an increase in central dopamine release.

Animals↗
PubMed1996

Elevated serum levels of S-100 after deep hypothermic arrest correlate with duration of circulatory arrest.

OBJECTIVE: Cerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and retrograde cerebral perfusion, are used to prolong the tolerated duration of circulatory arrest, and the latter may also decrease the possibility of air/particle embolization. The aim of the current study was to investigate whether the neurochemical marker S-100 is related to the duration of circulatory arrest, when the influence of embolic injury has been minimized by the use of retrograde cerebral perfusion during the last part of circulatory arrest. METHODS: Arterial serum levels of S-100 were followed before, during and after reconstructive surgery of the thoracic aorta during deep hypothermic arrest in ten adults. Retrograde cerebral blood perfusion was used during the latter part of the arrest period in eight of the ten patients. Neurologic status was followed daily. RESULTS: All patients survived the operation. The median (range) duration of cardiopulmonary bypass (CPB) was 184.5 (121-386) min. The median duration of circulatory arrest and retrograde cerebral perfusion was 50 (3-118) min and 16 (0-84) min, respectively. S-100 increased from 0.10 (0.02-0.18) microg/l preoperatively to 2.37 (0.64-10.80) microg/l after CPB (P<0.01), followed by a decrease to 0.79 (0.21-2.64) microg/l on the first postoperative day (P<0.01). The duration of circulatory arrest correlated with S-100 levels after CPB (r(S) = 0.71, P<0.05) and even better with the S-100 levels on the first postoperative day (r(S) = 0.83, P<0.01). However, there was no significant correlation between duration of arrest and duration of CPB. The duration of circulatory arrest without retrograde cerebral perfusion correlated well with S-100 levels on the first postoperative day (r(S) = 0.88, P<0.01), but not significantly with S-100 levels after CPB. CONCLUSIONS: S-100 levels after aortic surgery with deep hypothermic arrest correlate with the duration of circulatory arrest, indicating that the duration of circulatory arrest is damaging to the brain despite the use of deep hypothermia and partial retrograde cerebral perfusion. The highest correlation between S-100 and duration of arrest was seen on the first postoperative day. S-100 appears to perform well under clinical circumstances as a sensitive and discriminative marker for neuronal injury.

Adult↗
PubMed1996

Prognostic value of serum analyses of S-100 beta protein in malignant melanoma.

S-100 protein was first described in the central nervous system but is also present in malignant melanoma cells. Immunohistochemical detection of S-100 is widely used in the histopathological diagnosis of malignant melanoma. In the present study serum levels of S-100 beta protein were measured in 643 patients with cutaneous malignant melanoma. An immunoradiometric assay with three monoclonal antibodies against bovine S-100 protein beta subunit was used. At the time of blood sampling 553 patients were in clinical stage I, 24 in clinical stage II and 66 in clinical stage III. The overall survival rate was strongly associated with serum levels of S-100 protein. The observed/ expected death ratio was markedly increased with increasing levels of S-100 beta (P < 0.001). A fivefold increase in relative hazard was indicated by a value of S-100 beta exceeding 0.6 microgram/l (P < 0.001) and when this cut-off level was used S-100 beta had additional prognostic value independent of clinical stage (P < 0.001). Our data strongly suggest that S-100 beta in serum is an independent prognostic marker that may be useful in identifying high-risk cases and monitoring response to therapy in patients with malignant melanoma.

Adolescent↗
PubMed1995

On the quantitative structure-activity relationships of meta-substituted (S)-phenylpiperidines, a class of preferential dopamine D2 autoreceptor ligands: modeling of dopamine synthesis and release in vivo by means of partial least squares regression.

The quantitative structure-activity relationship between physicochemical properties and effects on dopamine (DA) synthesis and release in the rat brain, in a series of meta-substituted (S)-phenylpiperidines, has been investigated by means of partial least squares regression (PLS). The effect on DA synthesis caused by the drugs, in both non-pretreated and reserpine-pretreated rats, was assessed by measurements of tissue levels of L-DOPA accumulated in the striatum following treatment with a decarboxylase inhibitor. Assessment of effects on DA release was performed by analysis of perfusates collected from implanted microdialysis probes. The numerical characterization of the variation in physicochemical features of the phenylpiperidines used in the regression modeling was accomplished by using common tabulated aromatic and aliphatic substituent constants in combination with a set of property descriptors derived from molecular mechanics and semiempirical calculations. It was found that the biochemical responses could be accurately predicted by the regression models based on these molecular feature measures. The molecular features exerting influence on DA synthesis were found to be markedly different from those influencing DA release. This finding is discussed in terms of the possible existence of a dopamine receptor-mediated DA release-controlling mechanism, which may not involve the synthesis regulating DA D2 autoreceptor. Some findings regarding the impact of the piperidine N substituent on agonist properties of the drugs are reported. The regression models were also used for guidance in the search for a phenylpiperidine with a lower intrinsic activity, at the DA D2 type autoreceptor, than the partial DA agonist preclamol (3).

Animals↗
PubMed1995

Hypoalbuminemia in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Hypoalbuminemic patients admitted to the hospital for community-acquired pneumonia have increased mortality and morbidity. The aim of this study was to investigate the reasons for hypoalbuminemia in these patients. METHODS: During a 12-month period, all patients aged 50 to 85 years (with the exception of immunocompromised patients) with community-acquired pneumonia who were admitted to the Department of Infectious Diseases at Danderyd Hospital, Stockholm, Sweden, were included in a prospective study. The population studied consisted of 97 patients with a mean age of 69.6 years. The patients' nutritional status, including weight, history of weight loss, body mass index, and triceps skinfold thickness, was assessed on admission, as well as at two follow-up visits 8 weeks and 6 months after discharge from the hospital. Blood samples were drawn on admission, during the time in the hospital, and at the follow-up visits. Laboratory tests performed included the following: plasma proteins, albumin, transthyretin and transferrin, alpha 1-antitrypsin, orosomucoid, haptoglobin, C-reactive protein, and interleukin-6. RESULTS: No correlation was found between the serum albumin levels and the nutritional measurements. The serum albumin levels correlated positively with the transthyretin and transferrin levels, and inversely with the acute-phase proteins. CONCLUSIONS: The inflammatory reaction is the main reason for depressed serum albumin levels in elderly patients with pneumonia. The study results do not support the use of nutritional supplementation to alter the clinical outcome in these patients.

Aged↗
PubMed1995

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 1. Effects of substituents in the aromatic system on serotonin and dopamine receptor subtypes.

A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors.

Animals↗
PubMed1995

Acute dopaminergic influence on plasma adrenaline levels in the rat.

This study was aimed at in vivo characterisation of the possible role of dopamine receptors in the modulation of adrenaline release from the adrenal medulla in rats. Quinpirole (0.3, 1 and 3 mg/kg s.c., 30 min), an agonist at dopamine D2-like receptors induced a statistically significant increase not only in adrenal dopamine but also in plasma and heart adrenaline levels. The effects of the lowest dose of quinpirole were blocked by domperidone (5 mg/kg s.c., 150 min). Implantation of catheters followed by blood sampling appeared to be a stressful procedure, inducing itself an elevation of adrenal dopamine and of heart adrenaline by 100 and 250%, respectively. To explore the possibility of determining the plasma levels of adrenaline without blood sampling, regression modelling was performed by means of partial least squares regression (PLS) using treatment and levels of heart adrenaline and adrenal dopamine as predictor variables. The selected variables were found to be good predictors of plasma adrenaline levels. Accordingly, the increase in adrenal dopamine and heart adrenaline levels following administration of the dopamine autoreceptor agonist, talipexole, and the classical non-selective dopamine receptor agonist, apomorphine, were interpreted as indicators of the increased adrenomedullary adrenaline release. Neither of the dopamine D2 receptor antagonists used, i.e. domperidone, supposed to have only peripheral effects, nor raclopride, had significant effects on adrenal dopamine and heart adrenaline. Our results support the presence of peripherally located dopamine D2-like receptors, capable of acutely stimulating not only the synthesis of catecholamines, but also the release of adrenaline from adrenals in the conscious rat.

Adrenal Medulla↗
PubMed1995

Granulocyte/macrophage-colony-stimulating factor augments the induction of antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal antibodies.

A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n = 76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P < 0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15 micrograms/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P < 0.05). Moreover, patients with a high ab2 concentration (at least 15 micrograms/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P = 0.01).

Adolescent↗
PubMed1995

Pathologic fibrin formation and cold-induced clotting of membrane oxygenators during cardiopulmonary bypass.

In 1,800 patients undergoing cardiac surgery over a 2-year period, 11 incidents of abnormal inlet pressure elevations occurred before the membrane oxygenators. In 3 patients, the oxygenators had to be changed during cardiopulmonary bypass. This complication was found to be caused by fibrin formation possibly secondary to precipitation of fibrinogen with other coagulation factors in the heat exchangers of the oxygenators during the cooling phase. Large amounts of fibrin were demonstrated in the heat exchanger of the oxygenators. After careful washing of the apparatus, plasmin was added and fibrin was detected by measuring D-dimer levels. In heat exchangers from uneventful operations, only trace amounts of fibrin were found. Because there were no cold agglutinins demonstrated in the patients before surgery, cryoprecipitation studies were performed soon after surgery. When the patients' plasma samples were studied at different temperatures, from 37 degrees C down to 3 degrees C, cryoprecipitates or a gel (in 1 patient only) were formed. This indicated that there might be something abnormal with regard to fibrinogen-fibrin formation. The study patients were therefore investigated after the acute phase of the operation had ended for various coagulation factors, as well as for fibrin gel network characteristics. The results were compared with those of a control group (n = 10) with uneventful operations. There were no differences between the groups with regard to levels of coagulation factors VII and VIII and von Willebrand factor, although they were increased in both groups. The mean levels of coagulation inhibitors, antithrombin and Protein S, were slightly lower in the study patients. All of these patients had a highly pathologic, ie, tight fibrin gel network, except for the patient in whose sample a gel formed, despite being treated with aspirin or oral anticoagulants. The network was also tighter in some of the controls (v middle-aged reference individuals), although it was significantly tighter in the patients. It is concluded that some individuals who have an increased tendency to form tighter fibrin gel networks might be at increased risk for a severe complication during cardiac surgery performed under hypothermia.

Aged↗
PubMed1995

Effects of loratadine on anti-IgE-induced inflammation, histamine release, and leukocyte recruitment in skin of atopics.

The aim of this study was to assess the ability of the H1-receptor antagonist loratadine to modify anti-IgE-induced cutaneous wheal-and-flare and late-phase reactions (WFR and LPR), as well as histamine release and leukocyte accumulation in skin chambers. For this purpose, 10 atopics with allergic rhinitis were entered into a double-blind crossover study in which they received either placebo or loratadine (20 mg/day orally) for 8 days separated by a 7-day washout period. Blisters were induced on both forearms on day 7 of each treatment period, and were unroofed on day 8 and covered with plastic skin chambers. Chamber fluids were collected during 7 h after 1-h incubation with anti-IgE or control IgG. Intradermal challenge with histamine and anti-IgE was performed at the same occasion. As compared to placebo treatment, loratadine inhibited the immediate WFRs to anti-IgE by 35% (wheal) and 65% (flare), respectively (P < 0.01), and corresponding reactions to histamine challenge by 50% and 70% (P < 0.001), respectively. Moreover, the initial phase (0-2 h) of the LPR induced by anti-IgE was attenuated by up to approximately 60% (P < 0.001) during loratadine treatment. Thereafter, no inhibition of the LPR was observed. The magnitude and time course of histamine release into skin chambers was virtually the same after loratadine and placebo treatment, with a peak during 0-1 h and a progressive decline during the following 2 h. Accumulation of alpha 2-macroglobulin, reflecting extravasation of large plasma proteins, also peaked during the first hour and was unaffected by loratadine during the 8-h observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗