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Biomedical subjects

E Larsson

Publications and source records attributed to E Larsson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Concomitant single-dose and multiple-dose pharmacokinetics of terodiline in man, with a note on its enantiomers and major metabolites.

Single-dose and multiple-dose pharmacokinetics of terodiline were studied in 20 healthy volunteers by giving an initial oral dose of deuterium-labelled terodiline (12.5 mg or 25 mg) followed by multiple doses of Mictrol tablets (12.5 mg b.i.d. for 14 days and 25 mg b.i.d. for 14 days or vice versa). The enantiomer serum concentration ratio of S(-)/R(+) terodiline was close to unity at steady-state as well as during the disposition phase. The average single-dose kinetic parameters for the racemate after the 12.5 mg dose were: maximum serum concentration 41 micrograms/l, the corresponding time 3.4 hr, terminal half-life 61 hr, oral clearance 77 ml/min., renal clearance 12 ml/min. and apparent volume of distribution 382 1. The single-dose kinetics for the 25 mg dose and the multiple-dose kinetic parameters showed that linear kinetics prevailed. The average steady-state serum concentration was 275 micrograms/l at the lower dose and 509 micrograms/l at the higher dose. The degree of fluctuation during a dosage interval was 19% and the time to steady-state was about 9 days. The fraction unbound was about 8%. Unconjugated p-hydroxylated terodiline, p-hydroxy-m-methoxyterodiline and hydroxy-tert-butyl-terodiline constituted 15%, < 1% and 5%, respectively, of the terodiline steady-state levels.

Adult↗
PubMed1995

Can histopathological findings in early renal allograft biopsies identify patients at risk for chronic vascular rejection?

In order to assess the prognostic value of renal transplant biopsies for identifying patients at risk for chronic vascular rejection (CVR), 99 biopsies performed at 6 months after renal transplantation were evaluated as part of a prospective study. A chronic graft damage (CGD) score was calculated from the scores of vascular intimal hyperplasia, glomerular mesangial changes, focal lymphocytic infiltration, focal and diffuse interstitial fibrosis, and tubular atrophy, features compatible with CVR. The mean score for the whole patient population was 4.7 +/- 2.9 (range 0-11). There was a strong association between the CGD score at 6 months and the risk of graft loss up to 2 and 3 years following transplantation. Patients with a CGD-score of > or = 6 had a higher graft loss rate at 2 years than those with a score of < 6 (6/35 vs 2/54; p = 0.037). In patients with a functioning graft at 2 years, the CGD-score at 6 months correlated with graft function at 2 years. In addition to higher serum creatinine (p = 0.003) and lower GFR (p = 0.01), patients with a CGD-score of > or = 6 at 6 months also had a higher degree of albuminuria (p = 0.008) at 2 years as compared with patients with a CGD-score of < 6. At 3 years 10/35 patients with a CGD score of > or = 6 and 2/54 patients with a CGD-score of < 6 had lost their grafts (p = 0.002). The relative risk for graft loss associated with a CGD-score of > or = 6 was 7.65.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ischemia-induced transplant arteriosclerosis in the rat.

The effect of cold graft ischemia time on the development of transplant arteriosclerosis was investigated. Aorta grafts from DA or PVG rats were stored in a cold perfusion solution for 1, 4, or 24 hours before being orthotopically transplanted to PVG recipients. After observation times ranging from 2 to 8 weeks, the grafts were examined for various cell populations. Regional changes in the intima and media layers were measured by using an image analysis system. The arteriosclerosis-like changes seen in syngeneic grafts with the longest ischemia time could be almost as prominent as those seen in the allogeneic transplants. The magnitude of the regional intima changes in the syngeneic group correlated well with the ischemia time and in the allogeneic group with the observation time. The cell composition found in the intima and media of the allogeneic vessels consisted of macrophages, T-lymphocytes, MHC class II-expressing cells, and smooth muscle cells, whereas the syngeneic grafts contained almost exclusively smooth muscle cells and macrophages. We therefore conclude that the damage due to prolonged cold ischemia time is sufficient to cause pronounced graft arteriosclerosis. The pathophysiological mechanism leading to ischemia-induced arteriosclerosis is different from the one seen in the allogeneic situation.

Animals↗
PubMed1994

Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.

Platelet-derived growth factor (PDGF) affects the growth, migration, and function in vitro of mesenchymal cells, but little is known about its normal physiological functions in vivo. We show here that mice deficient for PDGF B die perinatally and display several anatomical and histological abnormalities. Kidney glomerular tufts do not form, apparently because of absence of mesangial cells. Instead, a single or a few distended capillary loops fill the glomerular space. The heart and some large arteries dilate in late-stage embryos. Most PDGF B mutant embryos develop fatal hemorrhages just prior to birth. Their hematological status includes erythroblastosis, macrocytic anemia, and thrombocytopenia. On the basis of these findings, we conclude that PDGF B has crucial roles in vivo in establishing certain renal and circulatory functions.

Anemia↗
PubMed1994

Association of a retrovirus with a wasting condition in the Swedish moose.

A wasting disease in moose (Alces alces) has killed more than one thousand animals in a densely populated, limited geographical area in Sweden. To investigate the cause, local environmental conditions were studied and infectious agents, mainly viruses, were looked for. A virus, identified as a retrovirus, has repeatedly been isolated from diseased animals by cocultivation of their leukocytes with fetal moose kidney cells. The virus has the characteristics of a member of the Oncovirinae subfamily, as deduced from its morphology from EM studies, reverse transcriptase activity, cell transforming properties, and serological cross-reactivity with other oncoviruses. Striking features of the disease are the poor and transient capacity of affected moose to respond serologically in addition to the frequent presence of high levels of reverse transcriptase activity in their sera.

Animal Diseases↗
PubMed1994

The effect of sucking habits, cohort, sex, intercanine arch widths, and breast or bottle feeding on posterior crossbite in Norwegian and Swedish 3-year-old children.

The upper and lower intercanine arch widths and the prevalence of posterior crossbite were registered for 445 3-year-old children with and without a continuing or previous dummy-sucking or finger-sucking habit in different areas in Sweden and Norway. Sami children from northern Norway also took part in the study, as well as 15 medieval skulls with intact deciduous dentitions. Compared with the nonsuckers, an increased prevalence of posterior crossbite was observed for the finger suckers, especially the Swedish girls. Stepwise logistic regression showed that posterior crossbite could be predicted with upper intercanine arch width alone. The finger sucking variable would not improve prediction; neither did other entities such as cohort (residential area), sex, lower intercanine arch width, nor the difference between upper and lower intercanine arch width. High prevalences of posterior crossbite were registered for dummy suckers (pacifiers) especially the Swedish girls (26%). Stepwise logistic regression showed that posterior crossbite in dummy suckers could be predicted with upper and lower intercanine arch width. Stepwise linear regression showed that both arches tended to be narrower in Swedes and girls, and that dummy sucking decreased the upper and increased the lower intercanine arch width. Analyses of covariance revealed that at least 2 years of dummy sucking is necessary to produce a significant effect in the upper jaw and 3 years in the lower jaw.

Bottle Feeding↗
PubMed1994

Altered localization and cytoplasmic domain-binding properties of tyrosine-phosphorylated beta 1 integrin.

We describe a novel approach to study tyrosine-phosphorylated (PY) integrins in cells transformed by virally encoded tyrosine kinases. We have synthesized a peptide (PY beta 1 peptide) that represents a portion of the cytoplasmic domain of the beta 1 integrin subunit and is phosphorylated on the tyrosine residue known to be the target of oncogenic tyrosine kinases. Antibodies prepared against the PY beta 1 peptide, after removal of cross-reacting antibodies by absorption and affinity purification, recognized the PY beta 1 peptide and the tyrosine-phosphorylated form of the intact beta 1 subunit, but did not bind the nonphosphorylated beta 1 peptide, the nonphosphorylated beta 1 subunit or other unrelated tyrosine-phosphorylated proteins. The anti-PY beta 1 antibodies labeled the podosomes of Rous sarcoma virus-transformed fibroblasts, but did not detectably stain nontransformed fibroblasts. The localization of the tyrosine phosphorylated beta 1 subunits appeared distinct from that of the beta 1 subunit. Adhesion plaques were stained by the anti-beta 1 subunit antibodies in Rous sarcoma virus-transformed fibroblasts plated on fibronectin, whereas neither podosomes nor adhesion plaques were labeled on vitronectin or on uncoated plates. Anti-phosphotyrosine antibodies labeled podosomes, adhesion plaques and cell-cell boundaries regardless of the substratum. One of the SH2 domains of the p85 subunit of phosphatidylinositol-3-kinase bound to the PY beta 1 peptide, but not to the non-phosphorylated beta 1 cytoplasmic peptide. Other SH2 domains did not bind to the PY beta 1 peptide. These results show that the phosphorylated form of the beta 1 integrin subunit is detected in a different subcellular localization than the nonphosphorylated form and suggest that the phosphorylation on tyrosine of the beta 1 subunit cytoplasmic domain may affect cellular signaling pathways.

3T3 Cells↗
PubMed1994

Presence of polymorphonuclear granulocytes during the early stage of transplant arteriosclerosis after prolonged ischemia in the rat.

The presence and function of polymorphonuclear granulocytes has been investigated, in particular, in the microcirculation in many short-term models of ischaemia/reperfusion injury. The aim of this study was to examine the presence of granulocytes in the aorta in a recently established long-term model of transplant arteriosclerosis, based on prolonged cold graft ischaemia time in the rat. Aortic grafts of PVG donors were subjected to two different cold ischaemia times of 1 and 4 h (n = 5 in each group) before an orthotopic transplantation to syngeneic recipients. The grafts were explanted shortly after various times post-reperfusion (7.5 min 24 h) and examined with conventional staining, immunohistochemistry and transmission electron microscopy for the presence of granulocytes. The results showed the presence of these cells adherent to the endothelial layer or in the subendothelial layer in grafts with both ischaemia times and with a maximum seen 2 h after transplantation. The internal elastic lamina was interrupted at sites of granulocyte adherence. We concluded that the polymorphonuclear granulocyte may be involved in the ischaemia/reperfusion injury in this model, thus, contributing to the development of accelerated transplant arteriosclerosis.

Animals↗
PubMed1994

Expression of an endogenous retrovirus (ERV3 HERV-R) in human reproductive and embryonic tissues--evidence for a function for envelope gene products.

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. It is expressed in several human tissues as LTR env spliced transcripts (9 and 3.5 kb). The highest level of expression is to be found in placenta and virus expression is down-regulated in choriocarcinoma cell lines. By means of in situ hybridization, the expression of ERV3 env was studied in selected human reproductive and embryonic tissues. It is concluded that (a) ERV3 env is expressed in syncytiotrophoblasts not only in the placenta but also in hydatidiform moles and choriocarcinomas (irrespective of origin) (b) ERV3 expression in placenta correlates to cell fusion but probably not to the fertilization process itself (c) ERV3 env is highly expressed in certain cells in spermatogenesis but not in the Sertoli or Leydig cells, and finally (d) ERV3 env is expressed in certain embryonic tissues such as the adrenal gland and nervous tissues.

Choriocarcinoma↗
PubMed1994

Total thyroidectomy in therapy-resistant Graves' disease.

BACKGROUND: Influences of total thyroidectomy have not been evaluated in patients with severe Graves' disease who might respond less satisfactorily to subtotal thyroid resection. METHODS: Thirty-three patients with Graves' disease underwent total thyroidectomy because of persistent endocrine ophthalmopathy (n = 28) or elevated thyrotrophin receptor antibody titers (n = 25) despite a mean of 2 years of thyrostatic therapy. Moreover, six and four patients had undergone radioiodine treatment and subtotal thyroid resection, respectively. Perioperative findings and complications have been investigated, as have influences on endocrine ophthalmopathy and thyrotrophin receptor antibody titers during a mean of 2.5 postoperative years. RESULTS: Total thyroidectomy substantiated mean thyroid weights of 17 gm, 2.3 hours of operating time, and total blood loss of 264 cc. Vocal cord paralysis and vitamin D-treated hypocalcemia occurred in two and three patients, respectively, and invariably persisted less than 6 months. Normalization of elevated thyrotrophin receptor antibody titers occurred in 86% of patients without radioiodine exposure, and stable or improved signs of endocrine ophthalmopathy were found in 96% of patients examined 6 or more months after the operation. CONCLUSIONS: Total thyroidectomy seems to be a surgically safe procedure in complicated Graves' disease and to provide normalization of therapy-resistant thyrotrophin receptor antibody titers. Because favorable influences might also encompass severe endocrine ophthalmopathy, prospective analysis on its efficiency is warranted.

Adult↗
PubMed1994

Artificial sucking habits: etiology, prevalence and effect on occlusion.

Active digit-sucking results in 1) reduced vertical growth of the frontal parts of alveolar process which creates an anterior open bite; 2) proclination of the upper incisors as a result of the horizontal force created by the digit; 3) anterior displacement of the maxilla for the same reason; 4) anterior rotation of the maxilla, resulting in an increased prevalence of posterior crossbite in the deciduous dentition; and 6) proclination or retroclination of the lower incisors which seems to be due to the strength of the tightness of the lower lip and tongue activity during sucking. When the sucking habit stops, the anterior open bite will correct itself spontaneously, due to increased growth of the alveolar processes, provided that the patient is still growing. If the lip activity and the lip/teeth relationship is normal, the upper incisors will upright themselves, and sometimes, due to the anterior displacement of maxilla, become somewhat retroclined. The skeletal effect of the sucking habit will remain. Improper use of a pacifier can create quite disastrous effects on the occlusion, if, for instance, the child has the shield. Otherwise, the effect of the pacifier is limited to the vertical and the transversal plane. The anterior open bite is normally more obvious and visible earlier in pacifier-suckers than in digit-suckers. As in digit-suckers, the open bite is associated with tongue-thrust during swallowing. Also in pacifier-suckers, the open bite will correct itself spontaneously when the habit stops despite the tongue-thrust. Sucking a pacifier is more clearly related to a posterior crossbite in the deciduous dentition than is digit-sucking. When the pacifier is in the child's mouth, the teat occupies the upper part of the anterior and middle part of the mouth thus forcing the tongue to a lower position. In the upper jaw, the teeth in the canine area lack palatal support from the tongue during the sucking activity of the cheeks. This reduces the arch width and increases the risk of a transversal malrelation between the upper and lower arches. The low tongue position widens the lower jaw in the same area thus enhancing the probability of the development of a posterior cross-bite.

Child↗
PubMed1993

Successive activation of the platelet-derived growth factor beta receptor and platelet-derived growth factor B genes correlates with the genesis of human choriocarcinoma.

The hydatidiform mole is a benign disease of the placenta characterized by the absence of the maternal genome. Approximately 3% of the reported cases will develop into malignant choriocarcinoma. In situ hybridization analysis reveals that the paternal platelet-derived growth factor (PDGF) beta receptor gene is up to 2 orders of magnitude more active in cytotrophoblasts of the complete hydatidiform moles than in normal placentae. The transition between hyperplasia (complete hydatidiform mole) and neoplasia (choriocarcinoma) in these cells correlates with at least a 10- to 20-fold activation of the PDGF-B gene. Since the neoplastic cytotrophoblasts have maintained an abnormally high level of PDGF beta receptor expression, we propose that a deregulated PDGF autostimulatory loop is involved in the genesis of human choriocarcinoma from hydatidiform moles.

Choriocarcinoma↗
PubMed1993

Postoperative analgesia and sedation following pediatric cardiac surgery using a constant infusion of ketamine.

Constant rate infusions of ketamine supplemented with intermittent doses of midazolam were given postoperatively to 10 children in order to provide analgesia and sedation during mechanical ventilation after cardiac surgery as well as during weaning from the ventilator and during spontaneous breathing. The aims of the study were to determine the pharmacokinetics of ketamine and evaluate the suitability of ketamine as an analgesic and sedative in postoperative pediatric cardiac patients. The children were between one week and 30 months old. Five children were given 1 mg/kg/h of ketamine and five children had 2 mg/kg/h. Blood was sampled during infusion and up to 24 hours after infusion for plasma concentrations of ketamine and the main plasma metabolite, norketamine, which were determined by gas chromatography and were compared to the degree of sedation. The children were arousable when ketamine concentrations were below 1.0 to 1.5 micrograms/mL. Plasma ketamine concentrations at steady state were within a narrow range for each infusion regimen and the calculated pharmacokinetic parameters were similar. Mean plasma clearance of ketamine was 0.94 +/- 0.22 L/kg/h. The elimination half-life was 3.1 +/- 1.6 hours, but in some children late samples indicated an even longer elimination half-life. Norketamine did not reach a steady state, but at the end of the infusion, the mean plasma concentration was higher than that of ketamine. The elimination half-life of norketamine was estimated to be 6.0 +/- 1.8 hours. Both ketamine infusion regimens were supplemented with midazolam and provided similarly acceptable analgesia and sedation during mechanical ventilation and during and after weaning from the ventilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗