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Biomedical subjects

E Eriksson

Publications and source records attributed to E Eriksson.

At least 199 records · Page 11Linked to original sources
PubMed1992

Effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on the prolactin suppression induced by a series of full and partial dopamine D2 receptor agonists in male rats.

The effect of pretreatment with a high dose of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (20 mg/kg, 24 h) on the intrinsic activity displayed by a series of full and partial dopamine D2 receptor agonists on prolactin regulating pituitary D2 receptors in male rats was studied. To increase baseline prolactin levels, gamma-butyrolactone in a dose inhibiting brain dopamine neurotransmission was given to all animals. In controls, i.e. rats not given EEDQ, supramaximal doses of all full and partial D2 receptor agonists tested decreased serum prolactin levels with greater than 80%. While the intrinsic activities of the dopamine precursor 1-DOPA and of the full agonists (+)-3-PPP, 5-OH-DPAT, B-HT 920 (talipexole), apomorphine, and NPA (R-(-)-N-n-propylnorapomorphine) were not affected by pretreatment with EEDQ, the effects of supramaximal doses of the partial agonists (-)-HW-165, TDHL (terguride), SDZ208-911, (-)-3-PP) (preclamol), and SDZ 208-912 were reduced to 66%, 74%, 59%, 100%, and 100%, respectively. The effect of EEDQ on the intrinsic activity displayed by the various agonists corresponds inversely to the intrinsic efficacy displayed by the drugs in other models of D2 receptor function with one exception only; thus, the prolactin suppressive effect of (-)-3-PPP was more effectively antagonized by EEDQ than would have been predicted from the intrinsic efficacy usually attributed to the drug. Since the dose of EEDQ used in the present study has previously been shown not to decrease D2 receptor density in the pituitary as measured using in vivo radioligand binding, it is suggested that alkylation of D2 receptors may change the conformation of the individual receptor complexes in a way that decreases the responsiveness to partial but not full agonists.

4-Butyrolactone↗
PubMed1992

Healing of partial thickness porcine skin wounds in a liquid environment.

This study employs a liquid-tight vinyl chamber for the topical fluid-phase treatment of experimental wounds in pigs. Continuous treatment with normal saline significantly reduced the early progression of tissue destruction in partial thickness burns. Uncovered burns formed a deep layer of necrosis (0.49 +/- 0.004 mm, mean +/- SD) although burn wounds covered with empty chambers demonstrated less necrosis (0.14 +/- 0.01 mm), fluid-treated wounds formed no eschar, and little tissue necrosis could be detected (less than 0.005 mm). Topical treatment with hypertonic dextran increased water flux across burn wounds by 0.24 ml/cm2/24 hr (mean, n = 95) over saline-treated wounds during the first 5 days after wounding. When partial thickness burn and excisional wounds were immersed in isotonic saline until healed, the daily efflux of water, protein, electrolytes, and glucose across the wound surface declined during healing to baseline values found in controls (saline-covered unwounded skin). The declining protein permeability was used as a reproducible, noninvasive, endogenous marker for the return of epithelial barrier function. Saline-treated excisional wounds healed within 8.6 +/- 0.6 days (mean +/- SD, n = 27) and burn wounds within 12.1 +/- 1.4 days (mean +/- SD, n = 15). Healing of fluid-treated wounds occurred without tissue maceration and showed less inflammation and less scar formation than healing of air exposed wounds (no attempt was made to compare rates of healing between air- and fluid-exposed wounds). We consider the fluid-filled chamber a potentially very useful diagnostic, monitoring, and delivery system for wound-healing research and for human wound therapy.

Animals↗
PubMed1992

Immunoreactivity with monoclonal antibody A-80 and nuclear DNA content in benign and malignant human breast disease.

Immunohistochemical analysis with the monoclonal antibody (MoAb) A-80, recognizing a tumor-associated cytoplasmic mucin-type glycoprotein, and cytometric nuclear DNA assessment were performed on 314 surgical specimens of the human mammary gland. The series included 36 benign conditions, 34 epithelial hyperplasias, 40 carcinomas in situ, and 204 primary invasive carcinomas. Normal breast parenchyma, benign tumors, and other nonmalignant lesions were all of DNA diploid (euploid) type and rarely expressed the A-80 glycoprotein. Differences in MoAb A-80 immunoreactivity and nuclear DNA content were noted among subtypes of epithelial hyperplasias. Fifteen of 34 epithelial hyperplasias were of DNA aneuploid type and the majority were A-80 immunoreactive. Of these 15 immunoreactive aneuploid epithelial hyperplasias, atypical intraductal hyperplasia was the most common subgroup. None of the 19 epithelial hyperplasias of DNA euploid type immunoreacted. Most of the intraductal (33 of 40) and invasive (180 of 204) carcinomas immunostained with MoAb A-80. The majority of the A-80 immunoreactive malignant tumors were of DNA aneuploid type (26 of 33 carcinomas in situ and 108 of 180 invasive mammary carcinomas). The results suggest that expression of the A-80 glycoprotein occurs at an early stage of malignant transformation. Genetically stable (euploid) mammary tumors seem to immunoreact with MoAb A-80 less frequently than genetically unstable (aneuploid) tumor variants. Combined analysis with MoAb A-80 and of nuclear DNA content in premalignant and malignant mammary lesions could be a useful tool of differential diagnostic and prognostic value.

Antibodies, Monoclonal↗
PubMed1992

Clomipramine effectively reduces premenstrual irritability and dysphoria: a placebo-controlled trial.

Forty nondepressed women displaying severe premenstrual irritability and/or dysphoria and fulfilling the DSM-III-R criteria of late luteal phase dysphoric disorder were treated daily for 3 menstrual cycles with either the potent serotonin reuptake inhibitor clomipramine (25-75 mg; flexible dosage) (n = 20) or placebo (n = 20). In both treatment groups premenstrual irritability and dysphoria (as rated daily by the patients using a visual analogue scale) were significantly reduced as compared with the rating during 2 pretreatment reference cycles; however, in the placebo group this reduction was only about 40% whereas, in the clomipramine group, the symptom decrease was greater than 80%. At all 3 treatment cycles, patients on clomipramine displayed significantly lower symptom rating than controls. Also with respect to the rating of global improvement, the results obtained with clomipramine were considerably and significantly better than those obtained with placebo. It is concluded that low doses of clomipramine effectively reduce premenstrual irritability and dysphoria with a response rate close to 100%. The possible role of serotonin in the pathophysiology of the premenstrual syndrome is discussed.

Adult↗
PubMed1992

[Current aspects of epidermal wound healing].

The multilayered cornifying epithelium of mammalian skin provides a barrier protecting the organism against external damage and preventing loss from the internal milieu. The unique features of the epidermis are responsible for its regenerative capacity. Basal keratinocytes are the stem cells for a vertical differentiation pathway during which an undifferentiated keratinocyte undergoes extensive changes into a keratinized flake of the horny layer. During epithelial repair the cells change their normal pattern of differentiation. Migratory activity and proliferation are the basis for the horizontal migration of the epidermal cells, which is inhibited by cell contact and completed by differentiation and keratinization. The mechanisms of cell activation and migration are currently under intense investigation. A large number of peptide growth factors have been shown experimentally to be active in wound healing. A better understanding of the molecular basis provides new perspectives for a more specific therapy in wound healing. Keratinocyte culturing has first been used in the treatment of large burns. Modifications try to include also dermal elements. Recent developments in molecular and cell biology indicate a perspective of cultured epithelial sheets containing genetically engineered keratinocytes for epithelial gene therapy.

Animals↗
PubMed1992

Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo-controlled trial.

A double-blind, placebo-controlled trial was undertaken to compare the effects of imipramine and clomipramine in the treatment of panic disorder with or without agoraphobia. The number of dropouts in the placebo-treated group was 7; in the imipramine-treated group, 4; and in the clomipramine treated group, 0. Ten subjects fulfilled the 12 weeks of treatment in the placebo group, 25 in the imipramine group, and 22 in the clomipramine group. To minimize dropouts because of side effects, a flexible dose regimen with a careful escalation of doses was applied. The maximal dose allowed was 250 mg/day. The mean (+/- SEM) daily doses reached were 124 +/- 9 mg (range, 50-250 mg) of imipramine and 109 +/- 8 mg (range, 25-200 mg) of clomipramine. At the end of the trial, the number of panic attacks as well as the anxiety between attacks (measured using the Hamilton Rating Scale for Anxiety) were markedly reduced in patients treated with either of the two antidepressant drugs, but only slightly decreased in patients on placebo. With respect to all major outcome parameters, i.e., full panic attacks, total number of anxiety attacks (full plus mild), and anxiety between attacks, the effect of clomipramine was clearly and significantly superior to that of imipramine (p less than 0.001, p less than 0.002, and p less than 0.002, respectively). Moderate intake of diazepam was allowed; in the clomipramine group (p less than 0.006), but neither in the imipramine group nor in the placebo group, a significant decrement in diazepam intake was observed during the course of the trial. The finding that clomipramine may have a higher potency and/or efficacy than imipramine in the treatment of panic disorder supports the concept that the antipanic effect of antidepressant drugs is due to the influence of these compounds on serotonergic rather than noradrenergic neurotransmission.

Adult↗
PubMed1992

Ear reconstruction.

This article discusses both the surgical and nonsurgical management of the burned ear. Partial and total autologous reconstruction, as well as osseointegrated prosthetic reconstruction, are described.

Burns↗
PubMed1991

Hemostatic responses to mental stress during the menstrual cycle.

To study the effect of sex hormones on the hemostatic responses to stress, blood samples were collected before, during, and after 20 min of mental stress from 9 healthy, non-smoking female volunteers, examined in the follicular and luteal phase. Mental stress caused significant increases in heart rate, blood pressure, and plasma catecholamines. In addition, analysis of variance indicated significant changes of leukocyte count, hematocrit, fibrinogen, von Willebrand factor antigen, t-PA activity and antigen in response to the stress test. However, in contrast to a male group previously investigated, there were no significant changes in factor VII coagulant activity in either menstrual phase. Overall the responses were more pronounced in the luteal as compared to the follicular phase. The findings support the concept that both gender and physiological variations in female sex hormones may modulate hemostatic responses to psychosocial stress.

Adult↗
PubMed1991

Higher postdexamethasone serum cortisol levels in agoraphobic than in nonagoraphobic panic disorder patients.

The dexamethasone suppression test (DST) was performed in panic disorder (PD) patients with (n = 32) or without (n = 31) agoraphobia and in normal controls (n = 49). Postdexamethasone serum cortisol levels were significantly higher in agoraphobic PD patients (105.3 +/- 19.3 nmol/L) both when compared to PD patients without agoraphobia (47.3 +/- 7.7 nmol/L; p less than 0.01) and when compared to healthy controls (51.7 +/- 8.3 nmol/L; p less than 0.01). The rate of nonsuppressors (i.e., subjects displaying postdexamethasone cortisol levels greater than 138 nmol/L) was 28% and 3% in agoraphobic and nonagoraphobic PD patients, respectively, and 12% in controls. In patients, the postdexamethasone cortisol levels did not correlate with the number of panic attacks per week, baseline anxiety as measured using the Hamilton Anxiety Scale, depressive symptoms as measured using the Montgomery-Asberg Depression scale, or duration of illness. Data from eight patients in whom a second DST was performed after treatment with imipramine or clomipramine for three months indicate that a marked reduction of the number of anxiety attacks is not necessarily accompanied by a normalization of a pathological DST. In conclusion, it is suggested that the elevated postdexamethasone cortisol levels sometimes observed in agoraphobic PD patients are more closely related to the agoraphobic behavior than to the panic attacks per se.

Adult↗
PubMed1991

Regional fibrinolysis following total hip replacement.

The local effect of operative trauma on the fibrinolytic system was studied in ten patients undergoing total hip replacement. Catheters were inserted in the femoral veins on both sides and blood was sampled from these catheters perioperatively. The following fibrinolytic variables were analysed in plasma and related to the different steps of surgery: tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI-1) activity. During surgery PAI-1 activity and t-PA antigen in the operated limb were significantly increased compared with preoperative values. There was a significant difference in PAI-1 activity and t-PA antigen between the operated and the non-operated limbs during surgery and within one hour postoperatively. During fixation of the femoral implant there was a significant difference between the operated and the non-operated limbs in t-PA activity. Thus the regional fibrinolytic response to trauma was dissociated from the response in the non-operated limb. The clinical relevance of the observed alterations in regional fibrinolysis, as related to thrombogenic mechanisms after hip surgery, remains to be elucidated.

Aged↗
PubMed1991

Effects of alpha 2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats.

Previous studies have shown that a low dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) reduces the density of alpha 2-adrenoceptors in rat cerebral cortex and antagonizes the effects of an alpha 2-adrenoceptor agonist on noradrenaline release in rat cortical slices. In the present study, a corresponding dose of EEDQ (1 mg/kg, s.c., 24 h) was shown to reduce the effect of the alpha 2-adrenoceptor agonists clonidine and guanfacine on noradrenaline turnover in rat brain while not affecting the inhibitory effect of clonidine on locus coeruleus (LC) cell firing. When considerably higher doses of EEDQ were administered (10 and 20 mg/kg, s.c., 24 h) not only the biochemical but also the electrophysiological effects of clonidine were markedly reduced (or even reversed). The data support the notion the EEDQ decreases the responsiveness of brain alpha 2-adrenergic receptors; moreover, they indicate that alpha 2-adrenoceptors regulating LC activity are characterized by a larger receptor reserve or are less sensitive to the influence of alkylation than are the population of alpha 2-adrenoceptors regulating noradrenaline utilization.

Animals↗
PubMed1991

Effects of the two partial D2 agonists (+)- and (-)-3-PPP on prolactin release in EEDQ treated male rats.

The effects of pretreatment with the irreversible inactivator of brain D2 receptors N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on the suppression of prolactin (PRL) release induced by the two partial D2 agonists (+)- and (-)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine [(+)-3-PPP, (-)-3-PPP] were investigated in gamma-butyrolactone (GBL) treated male rats. Pretreatment with a high dose of EEDQ (20 mg/kg, 24 h) did not influence the PRL response to (+)-3-PPP. In contrast, the effect of (-)-3-PPP was dose-dependently antagonized by EEDQ administration; thus, while pretreatment with EEDQ 2 mg/kg (24 h) failed to influence the efficacy of (-)-3-PPP, a complete antagonism of the PRL suppressive effect of the (-) enantiomer was obtained by administration of EEDQ 16 or 20 mg/kg (24 h). Moreover, in EEDQ (20 mg/kg, 24 h) treated rats (-)-3-PPP effectively antagonized the PRL inhibiting effect of the (+) enantiomer. Also, in EEDQ (20 mg/kg, 24 h) treated animals not receiving GBL (-)-3-PPP induced a dose-dependent increase in plasma levels of PRL. The data indicate that higher doses of EEDQ are required in order to reduce the responsiveness of lactotroph D2 receptors than that of various populations of brain D2 receptors. Also, the data lend support for the assumption that an altered receptor responsiveness may dramatically modify the response to a partial agonist with low intrinsic efficacy without affecting the response to a partial agonist with higher intrinsic efficacy.

4-Butyrolactone↗
PubMed1991

Pituitary and brain D2 receptor density measured in vitro and in vivo in EEDQ treated male rats.

The effect of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (20 mg/kg, 24 h) on dopamine D2 receptor density in rat pituitary and brain was measured using in vitro and in vivo radioligand binding techniques. In the in vitro radioligand binding experiments EEDQ was found to reduce the density (Bmax) of [3H]-spiperone binding sites in the striatum by 86% while in the pituitary the corresponding decrease was only 37%. The affinity (KD) of the remaining striatal and pituitary D2 receptors was not different in EEDQ treated animals as compared to controls. When D2 receptor density was measured in vivo the effect of EEDQ was less pronounced. Thus, in rats given EEDQ the specific binding of either of the two D2 ligands [3H]-raclopride or [3H]-spiperone (administered in a single dose) in striatum and in the limbic forebrain was reduced by 45-62%; moreover, no significant decrease in pituitary D2 receptor density was observed. The data are discussed in relation to the finding (presented in a separate paper) that the same dose of EEDQ that failed to influence pituitary D2 receptor density as measured in vivo effectively antagonizes the prolactin decreasing effect of the partial D2 agonist (-)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine [(-)-3-PPP].

4-Butyrolactone↗
PubMed1991

Impaired fibrinolysis and postoperative thromboembolism in orthopedic patients.

The incidence of deep vein thrombosis (DVT) and pulmonary embolism was studied prospectively in patients undergoing elective total hip replacement. 96 patients were randomly allocated to receive either low molecular weight heparin (LMWH) or unfractionated heparin (UFH). All patients had bilateral phlebography and pulmonary perfusion/ventilation scintigraphy 10-12 days after surgery. The following fibrinolytic variables were analysed in plasma and related to thromboembolism: tissue plasminogen activator (t-PA) activity, t-PA antigen (t-PA Ag), plasminogen activator inhibitor (PAI-1) activity and PAI-1 antigen (PAI-1 Ag). No significant difference was found, regarding the fibrinolytic response to surgery, between patients treated with LMWH and UFH. The level of PAI-1 activity was significantly increased before operation in patients developing DVT as compared to non-DVT patients (p less than 0.03). Immediately after surgery and in the morning the first postoperative day the levels of PAI-1 activity, PAI-1 Ag and t-PA Ag were positively correlated to thromboembolism. PAI-1 activity was the only preoperative fibrinolytic variable correlated to thromboembolism.

Aged↗
PubMed1991

Cerebrospinal fluid levels of monoamine metabolites in panic disorder.

The cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and the dopamine metabolite homovanillic acid (HVA) did not differ significantly in a group of patients with panic disorder (n = 17) as compared to age- and sex-matched normal controls (n = 17). While CSF concentrations of HVA and 5HIAA were significantly correlated in both patients and controls, CSF MHPG levels were significantly correlated with the concentrations of CSF 5HIAA and HVA only in patients. In a small number of subjects (n = 5), successful reduction of anxiety attacks by administration of clomipramine or imipramine (50-150 mg/day) for at least 2 months was associated with a significant decrease in CSF concentrations of 5HIAA and MHPG, but not HVA.

Adult↗