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Biomedical subjects

E Eriksson

Publications and source records attributed to E Eriksson.

At least 127 records · Page 7Linked to original sources

A naturalistic study of paroxetine in premenstrual syndrome: efficacy and side-effects during ten cycles of treatment.

Eighteen women with severe premenstrual syndrome (PMS) (premenstrual dysphoric disorder, PMDD) were treated openly with paroxetine for 10 consecutive menstrual cycles. Dosage was flexible (5-30 mg/day); also, the patients were free to chose between continuous medication and medication in the luteal phase only. The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period. Sedation, dry mouth, and nausea were common side-effects but declined during the course of the trial; in contrast, reduced libido and anorgasmia, which were reported by almost 50% of the participants, were not improved with time. The results indicate that the beneficial effects as well as the sexual side-effects of serotonin reuptake inhibitors persist unchanged for at least 10 consecutive cycles of treatment.

Adult↗

Electromyographic analysis of muscle fatigue in anterior cruciate ligament deficient knees.

The aim of this study was to detect possible differences in muscle fatigue and recovery of knee flexor and extensor muscles in patients with a deficient anterior cruciate ligament compared with patients with a normal anterior cruciate ligament. Surface electromyography of 15 patients with anterior cruciate ligament deficiency was performed while the muscles were under 80% of maximum isometric contraction, and after 1, 2, 3, and 5 minutes of rest. During the first 60 seconds of contraction, all muscles recorded significantly decreased mean power frequency and increased amplitude. The rate of decrease of mean power frequency was significantly greater in the injured quadriceps and normal hamstrings. All muscles except two recovered to the initial mean power frequency level after 1 minute of rest. All but two muscles in the injured and normal limb recorded an overshoot of mean power frequency during the recovery phase. This overshoot phenomenon also was seen for some muscles in the amplitude analysis. The findings confirm the fatigue state in all the muscles, suggest recruitment of more Type II fibers as the muscle fatigues, and show the physiologic adaptation of the quadriceps and hamstrings to anterior cruciate ligament insufficiency. The current study indirectly shows a dissociation between low intramuscular pH and mean power frequency during the recovery phase. It also indirectly suggests that the atrophied thigh muscles have fiber type composition similar to that of the normal side.

Adaptation, Physiological↗

Flap closure of postpneumonectomy empyema.

Empyema continues to be an uncommon, frustrating, and potentially lethal complication of pneumonectomy. Between 1990 and 1994 we treated 16 cases of recalcitrant postpneumonectomy (partial or total) empyema with combinations of pulse lavage, sharp debridement, muscle flaps, myodermal flaps, and thoracoplasty. We performed 11 pectoralis muscle flaps, 6 serratus anterior muscle flaps, 9 latissimus dorsi muscle flaps, 6 rectus abdominis muscle flaps, and 1 trapezius muscle flap for an average of 2.1 muscle flaps per patient. There was 1 omental flap. Of these flaps, 2 were free and the rest pedicled. Ten of the muscle flaps carried deepithelialized cutaneous paddles, and 6 were larger than 150 cm3. Thoracoplasty was done in 11 patients to decrease the volume of the postpneumonectomy empyema cavity. Of 16 patients, 4 failed initially because of persistent bronchopleural fistula or infection but resolved after one additional procedure. There was 1 perioperative death, 3 reoperations for bleeding, 1 patient with upper extremity deep vein thromboses, 1 seroma, and 1 patient with significant postoperative pain syndrome. In order to determine the efficacy of different operative approaches, patients were retrospectively divided into two groups according to the number of operations using flaps needed to resolve their postpneumonectomy empyema. Group A required only one operation using flaps to eliminate the postpneumonectomy empyema. Group B required two operations using flaps to remedy the postpneumonectomy empyema. Group B operations were further classified into B1, for the first operation, and B2, for the second operation. No patient needed more than two operations using flaps. Three significant variables were identified, the number of muscle flaps, the number of ribs in any thoracoplasty, and the preoperative serum albumin level. The A and B2 groups had significantly more muscle flaps transposed (p = 0.006) and ribs resected (p = 0.0002) than the B1 group. These findings suggest that filling the postpneumonectomy empyema space with muscle and collapsing any remaining space by thoracoplasty were the most successful strategy. The B2 group's average albumin level was significantly higher (p = 0.03) than that in either the A or the B1 group, suggesting that improved nutrition may have played a role in the lack of recurrence. Our goals of single-stage closure and decontamination of empyema cavities were best achieved by following these principles: removal of infected and necrotic tissue using sharp debridement and pulsed lavage, repair of bronchopleural fistulas with muscle flaps, and minimization of the dead space with combinations of muscle flaps and thoracoplasty.

Adult↗

Growth factors in the repair of partial thickness porcine skin wounds.

In 28 porcine partial thickness excisional wounds, the presence of several growth factors was first studied by enzyme-linked immunoadsorbent assay on wound fluid collected in sealed wound chambers. Basic fibroblast growth factor (bFGF) peaked on day 1 at 31.4 pg/ml; platelet derived growth factor (PDGF)-AB on day 3 reached 45.2 pg/ml, and transforming growth factor-beta (TGF-beta) on day 7 was 726.1 pg/ml. The same chamber system was used in 48 partial thickness excisional wounds for delivery of nanogram doses of bFGF, PDGF-AB, insulin-like growth factor (IGF)-1, epidermal growth factor (EGF), and cholera toxin. PDGF and EGF accelerated healing (1.1 days and 0.3 days, respectively), whereas bFGF and IGF-1 had no effect. Cholera toxin retarded healing by 1.9 days. Furthermore, in 100 excisional wounds EGF in the concentration range of 10 to 1,000 ng/ml had the same stimulating effect on healing. EGF at 10,000 ng/ml significantly delayed healing. The wound chamber model is useful for detecting of endogenous growth factors as well as for delivering exogenous factors.

Animals↗

Endothelial cell surface alkaline phosphatase activity is induced by IL-6 released during wound repair.

Phosphatase activity on endothelial cell surfaces is responsible, in part, for the conversion of adenosine nucleotides to adenosine, a potent vasodilator and anti-inflammatory mediator that can protect tissues from the ischemic damage that results from injury. To evaluate whether phosphatases are actively induced by a soluble factor released following injury, the effect of tissue fluids collected from porcine or human skin wounds was tested on primary cultures of endothelial cells. Phosphatase activity increased approximately 50-fold following 48-h culture in the presence of wound fluid. Inductive activity was present only in fluids collected during the inflammatory phase of wound repair. The phosphatase activity metabolized adenosine monophosphate to free phosphate and was the liver/bone/kidney alkaline phosphatase isoenzyme: activity was temperature- and levamisole-sensitive, 1-phenylalanine-resistant, and linked to the cell surface via phospholipid, and migrated at a size identical to this isozyme. interleukin-6 was identified as the phosphatase-inducing factor in wound fluid and the related cytokines, leukaemia inhibiting factor, and oncostatin M, caused a similar degree of alkaline phosphatase induction. Therefore, following injury, accumulation of interleukin-6 can lead to production by alkaline phosphatase of adenosine and subsequent protection from ischemic injury.

Adenosine Monophosphate↗

Analgesia following arthroscopy--a comparison of intra-articular morphine, pethidine and fentanyl.

It has recently been reported that morphine given in low doses intra-articularly can produce significant analgesia in patients undergoing arthroscopic knee joint surgery. Data are lacking on the effect of other opioids using a local approach for drug delivery. We studied the analgesic effect of intra-articular opioids in 70 patients, divided into 7 groups, subjected to arthroscopic knee surgery in general anesthesia. The dimension of the study was based on a power of 0.8 to detect a 25% difference in pain intensity between those receiving opioids locally versus systemically (alpha = 0.05 and beta = 0.20). Following surgery, but before terminating anesthesia, the patients received one of the following combinations: 1 mg morphine intra-articularly (i.art.) + saline intramuscularly (i.m.), 10 mg pethidine i.art + saline i.m., or 10 micrograms fentanyl i.art + saline i.m. In three additional groups the three opioids were given i.m. and saline given i.art. An additional control group received saline i.art. + i.m. We did not find any significant difference between the groups considering postoperative pain intensity, need for analgesics or considering time to standing/walking or to discharge, analysing each opioid independently. There was, however, a tendency for pethidine i.art. to produce the lowest pain scores both at rest and during movement (P = 0.06). If analysing the results with regards to if opioids were given intra-articularly or systemically, not considering the type of opioid given, we did however, find a significantly lower total sum of pain scores at movement following local administration (P < 0.05). No specific side-effects were detected. We conclude that pethidine given intra-articularly merits further investigation with respect to postoperative analgesia following the activation of peripheral opioid mechanisms.

Acetaminophen↗

Release of creatine kinase, troponin-T, and tissue plasminogen activator in arterial and coronary venous blood during coronary artery bypass surgery.

Tissue plasminogen activator (t-PA) as a possible marker of endothelial injury during elective coronary artery bypass surgery was studied. T-PA antigen and activity were measured in arterial and coronary venous plasma in 14 patients, and compared to the markers of myocyte injury creatine kinase (CK-MB) and troponin-T (TnT). Cardiopulmonary bypass (CPB) lasted 86 (55-107) min, and aortic cross-clamping (cold, crystalloid cardioplegia) lasted 41 (25-62) min (median (central 90% percentile)). Blood flow in the great cardiac vein was measured by retrograde thermodilution, and increased from 49 (27-90) ml/min before CPB to a maximum of 92 (55-125) ml/min 40 min after declamping (not significant). CK-MB, TnT, and t-PA antigen and activity all increased during CPB, and were significantly higher in coronary sinus than arterial plasma after declamping the aorta. Net cardiac release ([coronary sinus-arterial concentration] x coronary flow) of TnT increased after the aorta was declamped, and was higher in the seven patients with the longest cross-clamping time than in the seven with the shortest time (p < 0.01). Cardiac release of CK-MB and t-PA antigen also increased after declamping, but with no significant difference between long and short cross-clamp times. t-PA activity, however, increased more in the patients with the longest cross-clamp times (p < 0.008). In conclusion, CK-MB, TnT and t-PA were released from the postcardioplegic heart. Release of t-PA indicates that postcardioplegic coronary endothelial activation or injury occurred t-PA activity as well as TnT increased more in patients with long times of cross-clamping, indicating that t-PA activity may be a possible marker of postcardioplegic endothelial injury or activation.

Aged↗

Measurement of fibrinolytic components in human tissue.

The fibrinolytic system is involved in the resolution of thrombi and in tissue repair. Quantitation of the activators and inhibitors of this system at tissue level is crucial to further characterise these processes. Hitherto, there have been difficulties in measuring the individual components of the plasmin system in human vascular and peritoneal tissue. The aim of this study was to develop a protocol allowing quantitation of activators and inhibitors of plasmin generation at the tissue level. Following a strict protocol in the processing of tissue, the efficiency of extraction in tissue homogenisates was compared using buffers containing acetic acid, 1% Triton X-100 and thiocyanate. The influence of different modalities of normalisation was investigated by normalising to wet weight, total protein content, protein content in supernatant or DNA. Using the protocol, all buffers extracted components of the plasmin system sufficiently for detection. The acetic acid buffer yielded the greatest amount of protein, and in extracting plasminogen activators was comparable to the thiocyanate buffer and significantly more efficient than the Triton buffer (p < 0.05). The relationship between the individual components was unaltered by different means of normalisation. The protocol described, using an acetic acid buffer and normalising to wet weight, seems to be a simple and efficient technique for measuring components of the fibrinolytic system, at least in the tissues investigated.

Blood Vessels↗

Release of markers of myocardial and endothelial injury following cold cardioplegic arrest in pigs.

Cold cardioplegic arrest causes reperfusion injury to both endothelium and myocardium. We investigated release of troponin-T (TnT), tissue plasminogen activator activity (t-PA) and histamine (HA) from the heart before and after 2h of cold crystalloid cardioplegia in eight Swedish landrace pigs. Coronary sinus blood flow was measured in an external shunt between the coronary sinus and the right atrium. TnT, t-PA and HA were measured concomitantly in arterial and coronary sinus plasma, and the cardiac release was calculated. Cardiac release of TnT increased from 18 (15-25) micrograms/min (median (central 90% percentile)) before cold cardioplegia to maximum 281 (132-510) micrograms/min 30 min after aortic declamping (p < 0.02 vs initial value). t-PA rose from -4 (-52-34) to maximum 249 (75-691) IU/min 2 min after declamping (p < 0.01) and thereafter returned to baseline levels. The net cardiac release of HA was 72 (-80-1321) nmol/min before cardioplegia, rising to 234 (-188-524) after 2 min of reperfusion (p < 0.02) and returning to baseline after 30 minutes. We conclude that the porcine heart releases t-PA, Tn-T and HA during postcardioplegic reperfusion. The differing kinetics of their release may indicate different affection of the myocardium and the endothelium. Tn-T, t-PA and HA are potential markers of myocardial and endothelial injury in the porcine heart.

Animals↗

Assessment of homogeneity in polypeptide expression in breast carcinomas shows widely variable expression in highly malignant tumors.

We describe the results from a protein-based approach to the study of heterogeneity in gene expression between human tumors. Cell preparations from 5 benign breast lesions, 5 potentially weakly malignant and 4 potentially highly malignant invasive ductal breast carcinomas were examined by 2-dimensional gel electrophoresis (2-DE) gels. Qualitative and quantitative differences were recorded by computerized analysis. Analysis of samples from different areas of the same tumor showed a high degree of similarity in the pattern of polypeptide expression. Analysis of 2 tumors and their metastases revealed similar 2-DE profiles. In contrast, variations between different lesions with comparable histological characteristics were considerable. Greater differences in polypeptide expression were observed between potentially highly malignant carcinomas compared with comparisons of less malignant lesions. Our results show that malignant human breast carcinomas may be highly heterogeneous in their patterns of gene expression.

Adult↗

Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing.

The restoration of functional connective tissue is a major goal of the wound healing process. This regenerative event requires the deposition and accumulation of collagenous and noncollagenous matrix molecules as well as the remodelling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs). In this study, we have utilized substrate gel electrophoresis, radiometric enzyme assays, and Western blot analyses to determine the temporal pattern of appearance and activity of active and latent MMPs and their inhibitors during the entire healing process in a partial thickness wound model. Through the use of substrate gel electrophoresis, we studied the appearance of proteolytic bands whose molecular weight was consistent with their being members of the MMP family of enzymes. Proteolytic bands whose molecular weight is consistent with both the active and latent forms of MMP-2 (72 kDa, Type IV gelatinase) were detected in wound fluid of days 1-7 after wounding. The number of active MMP-2 species detectable in wound fluid was greatest during days 4-6 after wounding. The most prominent proteolytic band detected each day migrated with a molecular weight consistent with it being the latent form of MMP-9 (92 kDa, Type V pro-collagenase). In contrast to MMP-2, the active form of this enzyme was never detected. The presence of MMP-1 (interstitial collagenase) was detected by immunoblot in the wound fluid from days 1-6 post-injury. Using a radiometric enzyme assay for collagenase inhibitory activity we have also determined the time course of activity of endogenous matrix metalloproteinase inhibitors. We have correlated these data to the known cellular events occurring in the wound during this time period as well. This study establishes a prototypical pattern of MMP appearance in normal wound healing. It may also provide potential intervention sites for the therapeutic use of inhibitors of aberrant MMP activities which characterize chronic wounds.

Animals↗

A prospective controlled randomized study of arthroscopic lavage in acute primary anterior dislocation of the shoulder: one-year follow-up.

Traumatic primary anterior shoulder dislocation has a very high recurrence rate among young people. This has supplied the motivation for studies to find methods of treatment that might become an alternative to traditional therapy. A prospective controlled study was performed to test the hypothesis that acute arthroscopic lavage might have a positive effect on recurrence rate as well as on shoulder stability, range of motion and mobilization. 30 consecutive patients between 18 and 30 years of age were randomized into 2 groups, 1 control group treated conservatively and 1 group treated with acute arthroscopic lavage within 10 days. Clinical examination was made by an independent observer at 1, 6 and 12 months. Results at 6- and 12-month check-ups showed a statistically significantly lower rate of redislocation and a wider range of motion for the group treated with acute arthroscopic lavage. Functional assessment according to the Lysholm shoulder score also indicated better functioning of the joint. Our 1-year follow-up shows very promising and interesting results.

Adult↗

MRI examination of the glenohumeral joint after traumatic primary anterior dislocation. A descriptive evaluation of the acute lesion and at 6-month follow-up.

Primary traumatic anterior dislocation of the shoulder in young patients has a high recurrency rate. There are varying opinions on the pathology behind the recurrences. The aim of this study was to describe the MRI characteristics of the acute lesion, and at 6-month follow-up. Thirty patients aged 18-30 years with primary traumatic anterior dislocation of the shoulder were randomized into two groups. One group was treated with acute arthroscopic lavage within 10 days. The control group was treated with traditional non-operative therapy. All patients underwent acute MRI within 10 days and before the arthroscopic lavage, and again at the 6-month follow-up, for evaluation of the lesions. The acute MRI verified Hill-Sachs lesions in all patients. At the 6-month follow-up MRI, there was no change in the size of the Hill-Sachs lesion. This was also the case with the six patients in the control group with recurrent dislocations during the first 6 months. Twenty-nine patients (97%) had joint effusion at the acute MRI, which was very useful for evaluation of the soft tissue pathology. The glenohumeral ligaments were detached in 20/30 patients (66%), and the labrum in 22/30 patients (70%). A capsulolabral detachment classified as a Baker 3 lesion was seen in 16/30 (53%) of the patients, including all six patients with recurrent dislocation. At the 6-month control only 3/30 (10%) of the patients had joint effusion for adequate evaluation of the labrum and ligamentous pathology. A Hill-Sachs lesion was found in 100% of the patients after primary dislocation, and recurrent dislocations did not change the size of the lesion. The study supports the opinion that this lesion is overlooked in the clinical situation. The joint effusion at the acute MRI was of utmost importance for evaluation of the soft tissue pathology. The 6-month MRI control was therefore considered inconclusive when evaluating capsulolabral lesions, due to lack of effusion. MRI arthrography with contrast administration would have been very helpful at the 6-month examination.

Adolescent↗

Inverse agonism at dopamine D2 receptors. Haloperidol-induced prolactin release from GH4C1 cells transfected with the human D2 receptor is antagonized by R(-)-n-propylnorapomorphine, raclopride, and phenoxybenzamine.

Our earlier observation that the antipsychotic drug haloperidol in the absence of dopamine increases cAMP formation and prolactin release in two prolactin-producing cell lines expressing rat dopamine D2 receptors (GH3, GH4ZR7), but not in similar cells devoid of D2 receptors (GH4C1), prompted us to suggest that haloperidol may act as an inverse (or negative) agonist, rather than as a neutral antagonist, at the D2 receptor (Nilsson and Eriksson 1993). In the present study it is shown that haloperidol elicits a dose-dependent increase in prolactin release also in prolactin-producing GH4C1 cells transfected with the human dopamine D2 receptor (short isoform) (GH4C1-hD2s); in addition, it is shown that another antipsychotic drug, flupenthixol, also causes prolactin release per se in this cell line. The effect of haloperidol on prolactin release in GH4C1-hD2s is calcium dependent and counteracted by pretreatment either with the D2 receptor agonist R(-)-n-propylnorapomorphine or with a D2 receptor antagonist that does not affect prolactin release per se (raclopride). In addition, pretreatment with the alkylating compound phenoxybenzamine at a concentration causing a marked reduction of D2 receptor density in GH4C1-hD2s cells significantly counteracted haloperidol-induced prolactin release.

Animals↗

Fibrinolysis in human peritoneum during operation.

BACKGROUND: A reduced local fibrinolysis seems to be an important mechanism in the formation of adhesions. Peritonitis may cause adhesions, and the aim of the present study was to determine peritoneal fibrinolytic capacity in inflamed and normal peritoneum. METHODS: Biopsy specimens from normal and inflamed human peritoneum were taken at the beginning and end of operation. After extraction plasminogen activator activity (PAA) was determined by using a chromogenic substrate assay in the presence or absence of inhibitory antibodies against tissue-type plasminogen activator (t-PA), urokinase or plasminogen activator inhibitor-1. RESULTS: t-PA exerted 95% of the PAA. PAA was significantly reduced (p < 0.01) during peritonitis (3.0 IU/micrograms protein; range, 0.3 to 4.2) compared with normal peritoneum (7.1 IU/micrograms protein; range, 0.6 to 18.1). A significant reduction (p < 0.05) in PAA occurred during operation both in normal peritoneum (3.8 IU/micrograms protein; range, 0.8 to 8.6) and in peritonitis (0.6 IU/micrograms protein; range, 0.16 to 2.1). Values are given as medians. CONCLUSIONS: The main PAA in human peritoneum was t-PA. The activity was decreasing during operation and reduced in peritonitis. This reduction in PAA might be a local response to inflammation.

Abdomen↗

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins.

Malignant progression of tumour cells is caused by the accumulation of genetic defects, which when combined will generate a large phenotypic diversity. Simultaneous quantitation of a large number of gene products in tumour cells is desirable, but difficult to achieve. We have here quantitated the levels of a number of abundant polypeptides in human breast carcinoma cells using two-dimensional gel electrophoresis (2-DE; PDQUEST). For this purpose, tumour cells were prepared from the tissue of 17 breast carcinomas. Fibroadenoma tissue was used as reference for benign cells. An increase of the spot density of the PCNA polypeptide was observed in rapidly proliferating tumour cells, confirming the validity of the procedures used. In the set of 24 polypeptide spots with known identity, decreases in cytokeratin and tropomyosin levels were observed. The levels of all cytokeratin forms resolved (CK7, CK8, CK15 and CK18) were significantly lower in carcinomas than in fibroadenomas. The levels of tropomyosin 2 and 3 were lower in carcinomas than in fibroadenomas. In contrast, the levels of some members of the stress protein family (pHSP60, HSP90 and calreticulin) were higher in carcinomas. Furthermore, changes in the expression of lactate dehydrogenase and GT-pi, but not in nm23, were observed. We conclude that simultaneous analysis of multiple polypeptides in human carcinomas can be achieved by 2-DE and may be useful in prognostic studies, and that malignant progression of breast carcinomas results in the decreased expression of cytokeratin polypeptides. This phenomenon must be considered in studies where cytokeratins are used as markers to identify the epithelial cell compartment in breast carcinomas.

Breast Neoplasms↗

Treatment of chronic, nonhealing abdominal wound in a liquid environment.

A 66-year-old woman with an abdominal wound caused by infected synthetic mesh had failed to heal in spite of many surgical attempts to close the wound. A sealed transparent vinyl chamber was glued to the periphery of the wound and antibiotics in high concentrations (up to 2,500 times the minimum inhibitory concentration) were delivered through the chamber. The wound fluid in the chamber was used for analysis of microbial activity, concentration of residual antibiotics, and growth factor activity. After 10 weeks of treatment, the wound was closed and has not recurred in 24 months.

Abdominal Injuries↗

Wound fluid-derived heparin-binding EGF-like growth factor (HB-EGF) is synergistic with insulin-like growth factor-I for Balb/MK keratinocyte proliferation.

Epidermal cell proliferation is required for re-epithelialization during wound repair. Re-epithelialization of partial thickness excisional wounds in pigs is complete by 6 days after injury. The presence of insulin-like growth factor-I (IGF-I) and heparin-binding molecules that are mitogenic for keratinocytes was examined in wound fluid obtained daily from these wounds. Two significant heparin-binding growth factor activities for Balb/MK keratinocytes were detected, a major one that was eluted from a heparin affinity column with 1.1 M NaCl and a minor one with 0.5 M NaCl. These activities appeared 1 day after injury, were maximal by 2-3 days later, and disappeared by 6 days after injury. The molecule eluting with 1.1 M NaCl was heparin-binding EGF-like (HB-EGF). The levels of IGF-I in wound fluid were 45-90 ng/ml during the first 3 days following injury, decreased thereafter, and were not detectable 6 days after injury. IGF-I at 100 ng/ml, increased HB-EGF mitogenic activity for Balb/MK keratinocytes by 40-50 fold. We conclude that the synergism between IGF-I and HB-EGF and their relative concentration at the various days after injury may be important variables for regulating re-epithelialization during wound repair.

3T3 Cells↗