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Biomedical subjects

T Henriksen

Publications and source records attributed to T Henriksen.

At least 19 recordsLinked to original sources

[HELLP syndrome--4 case reports].

HELLP-syndrome (H - haemolysis, EL - elevated liver enzymes, LP - low platelet count) is a serious complication of pregnancy. It can be considered as a variant of severe preeclampsia, where haemolysis, hepatic damage (elevated liver enzymes) and thrombocytopenia (low platelets) are all present. Four case reports of HELLP-syndrome are described. HELLP-syndrome may develop within a few hours. It can be seen pre-, intra- and postpartum. Many patients do not exhibit a clinical picture of severe preeclampsia. Patients who develop HELLP-syndrome usually complain of malaise, nausea, epigastric pain and headache. The diagnosis is confirmed when haemolysis, elevated liver enzymes and thrombocytopenia are demonstrated. Patients with HELLP-syndrome require intensive care by a team of obstetricians, anaesthesiologists and haematologists.

Adult

[The vascular endothelium--a multifunctional organ].

The authors summarize the role of the vascular endothelium in hemostasis, thrombosis, vasomotor regulation, inflammation and angiogenesis. Quiescent endothelium is antithrombogenic, whereas perturbed endothelial cells become thrombogenic. The endothelium produces both vasodilating substances like endothelial derived relaxing factor and prostacyclin and vasoconstrictive compounds such as the endothelins. The presence of leucocyte adhesion molecules on the endothelial surface allows specific interactions with circulating leucocytes. Surface expression of HLA-antigens class I and II further underscores the importance of the endothelial cells in the inflammatory process. In the recent years it has become evident that the endothelial cells play a major role in the pathogenesis of diseases such as atherosclerosis, preeclampsia, hemolytic uremic syndrome and certain vasculitides.

Arteriosclerosis

Increased lipolytic activity and high ratio of free fatty acids to albumin in sera from women with preeclampsia leads to triglyceride accumulation in cultured endothelial cells.

OBJECTIVE: The null hypothesis of this study was that the triglyceride accumulation in endothelial cells exposed to sera from preeclamptic women was determined by the presence of triglyceride-rich lipoproteins in the sera. STUDY DESIGN: The accumulation of triglycerides in cultured endothelial cells was studied using incorporation of tritiated glycerol. RESULTS: Triglyceride-rich lipoproteins in the patient sera contributed little to the endothelial triglyceride accumulation. However, sera from preeclamptic women were found to have a higher molar ratio of free fatty acids to albumin compared with sera from women with normal pregnancies (1.6 +/- 0.5 vs 0.9 +/- 0.4, respectively, p less than 0.025). In addition, sera from preeclamptic women, compared with sera from normal pregnancies, showed enhanced lipolytic activity (release of free fatty acids 0.85 +/- 0.29 vs 0.17 +/- 0.16 mmol/ml per 24 hours, respectively; p less than 0.025) that further increased the free fatty acids/albumin ratio. CONCLUSION: Sera from preeclamptic women have both a higher ratio of free fatty acids to albumin and increased lipolytic activity, resulting in enhanced endothelial uptake of free fatty acids, which are further esterified into triglycerides.

Cells, Cultured

Sera from preeclamptic women increase the content of triglycerides and reduce the release of prostacyclin in cultured endothelial cells.

UNLABELLED: The causes of the "endothelial dysfunction" accompanying preeclampsia are unknown. Women with preeclampsia have a marked hyperlipidemia which reflects altered lipid metabolism. We asked if the hyperlipidemic sera of preeclamptic women could cause altered endothelial cell properties. Cultured endothelial cells were incubated with sera from women with preeclampsia (PE) or normal pregnancies as controls. Fifty PE-sera were tested and in 45 cases the endothelial cells acquired a large number of sudanophilic granules which by electron microscopy had lipid appearance. In 31 incubations with 31 individual control sera cellular lipid granules were observed in 4 cases. The cellular triglyceride content was increased to 153 +/- 30 compared to 48 +/- 10 micrograms/mg cell protein in the control cells. Furthermore, the endothelial release of prostacyclin, measured as 6-keto PGF1 alpha, was 8.8 +/- 0.6 ng/mg cell protein in cells incubated with PE-sera as compared to 40.3 +/- 6.4 ng/mg in the control cells. CONCLUSION: The hyperlipidemic sera from preeclamptic women induced triglyceride accumulation in cultured endothelial cells. This was accompanied by altered endothelial function as demonstrated by reduced prostacyclin release.

6-Ketoprostaglandin F1 alpha

Epithelial cells from human fallopian tube in culture.

The epithelial cells lining the inner surface of the Fallopian tube influence the reproductive process by both their ciliary and secretory activities. The aim of the present work was to establish a method to culture these cells as a model for more specific studies of their properties. Minor slices of the mucosal ridges were cut and minced extensively using a fine scissor. The resulting pieces were washed once, resuspended in RPMI 1640 with 20% fetal calf serum and seeded in plastic dishes. After 2 days, the medium was replaced with RPMI 1640 containing human albumin, insulin and transferrin. Seven to 10 days later, the cell number had increased 5-8 times in 70% of the cultures. The identity of the cells was assessed after 1-3 weeks in culture. Of the cells, 98% stained positive for the antibody to epithelial cell-specific protein cytokeratin. Electron microscopic studies of the cultures showed epithelial characteristics including cilia, microvilli and intercellular junctions in the form of desmosomes. The cells could be kept in culture for 6-8 weeks. In conclusion, a method to culture epithelial cells from the human Fallopian tube is described. The cells have been identified and they can be kept in culture for 6-8 weeks in quantities sufficient for experimental use.

Cells, Cultured

Ultraviolet-radiation and skin cancer. Effect of an ozone layer depletion.

The effect of changes in the ozone layer on the incidence of skin cancer was explored using data for Norway. Attempts were made to arrive at a relationship between the "environmental effective UV-dose" and the skin cancer incidence. Norway is well suited for this purpose because of the large variation in the annual UV-dose from north to south. Furthermore we have a well developed cancer registry and a homogeneous population with regard to skin type. Four different regions of the country, each with a broadness of 1 degree in latitude (approximately 111 km), were selected (located around 69.5, 63.5, 60 and 58.5 degrees N). The annual effective UV-doses for these regions were calculated, assuming normal ozone conditions throughout the year and the action spectrum proposed by CIE, which extends up to 400 nm. The incidence rate (in the period 1970-1980) of malignant melanoma and non-melanoma skin cancer (mainly basal cell carcinoma) increased with the annual environmental UV-doses. For both these types of cancer a quadratic dose-effect relationship seems to be valid to a first approximation. The present data indicate that the incidence of skin cancer would increase by approximately 2% for each percent ozone reduction.

Humans

The source of cholesterol for progesterone synthesis in cultured preovulatory human granulosa cells.

There are three possible sources of cholesterol for immediate use in progesterone production by preovulatory human granulosa cells: follicular fluid high-density lipoprotein, de novo synthesis of cholesterol, and performed intracellular cholesteryl ester stores. In the present study these three alternatives were investigated. First, an in vitro model was established that mimics the preovulatory environment, including short-term cultures and use of autologous follicular fluid in the culture medium, instead of serum. Using this model it was found that the presence of high-density lipoprotein from follicular fluid in the culture medium did not affect the synthesis of progesterone by the granulosa cells. Next, addition of inhibitors of de novo sterol synthesis, like low-density lipoprotein, 25-OH cholesterol and compactin to the culture medium, did not reduce [14C]acetate incorporation into sterols and steroids by the cells. The sterol synthesis was accordingly interpreted to be at a low and therefore uninhibitable level. Finally, the content of free and esterified cholesterol in freshly isolated granulosa cells was found to be 50 +/- 7 and 52 +/- 13 pmol/mg cell protein, respectively. We suggest that neither follicular high-density lipoprotein nor endogenous synthesis is the immediate cholesterol source for the progesterone production in preovulatory human granulosa cells. However, granulosa cells have a large store of cholesteryl esters that may provide free cholesterol for the preovulatory progesterone production.

Aminoglutethimide

Biological amplification factor for sunlight-induced nonmelanoma skin cancer at high latitudes.

Data for the incidence of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin, registered for six regions of Norway during 10 years (1976-1985), were used to evaluate the biological amplification factor Ab for induction of these cancers by sunlight. Ab is the ratio of the increment in skin cancer production to the increment in causative sunlight exposure. Two different approximations were used for the action spectrum for carcinogenesis: an erythema action spectrum; and an action spectrum for mutagenesis of cells in the basal layer of the skin. These two fundamentally different approaches yielded Ab values that were similar to within about 10%: 2.1-2.3 for BCCs; and 1.6-1.8 for SCCs. Using a radiation amplification factor for ozone depletion of 0.8-1.1, we find that the total amplification factor for BCCs is within the range 1.6-2.1 and that that for SCCs is within the range 1.3-1.7 at northern latitudes of 60-70 degrees. Thus, an ozone depletion of 1% will result in an increase in the incidence of BCCs by 1.6-2.1% and of SCCs by 1.3-1.7%. There were no significant differences between the values for men and women. Neither was there any significant difference between Ab values found for skin commonly exposed to sunlight (face) and for skin sites normally covered by clothes and therefore receiving much lower exposures, in spite of the fact that the tumor density per unit skin area was a factor of 20 or more larger at the former sites. This observation, as well as the curves relating cancer incidence with annual exposure to carcinogenic sunlight, supports a power law relationship between cancer incidence and annual sun exposure. Sunlight appears to be the main cause of BCCs and SCCs even at the high latitudes of Northern Norway. All over, BCCs were found to be about 6 times more frequent than SCCs. The ratio of the incidence of BCCs to that of SCCs seemed to be independent of the latitude. Finally, BCCs were found to be equally frequent among men and women, while SCCs were found to be about twice as frequent among men as among women.

Basal Cell Carcinoma

Ozone depletion and its consequences for the fluence of carcinogenic sunlight.

A slight reduction of the ozone level over the northern hemisphere in the period 1969-1986 has been reported [D. Lindley, Nature (Lond.), 323: 293, 1988]. Ozone measurements performed in Oslo are in agreement with this. However, the ozone level for 1987 and 1988 was above normal, and no negative or positive trend is apparent for the last 10 years. The consequences of an ozone reduction for the fluence rate of carcinogenically effective sunlight was evaluated on the basis of recent action spectra for mutagenesis in cells, carcinogenesis in mice, and erythema induction in humans. Depending on the choice of action spectrum we find amplification factors (defined as percentage increase in yearly fluence of carcinogenically efficient sunlight per percentage reduction of the ozone level) between 1.1 and 1.3 at latitudes between 0 and 20 degrees and between 0.9 and 1.1 for Northern Europe. These estimates are significantly lower than 2.0, which is the value found when the calculations are based on the DNA absorption spectrum (R. B. Setlow, Proc. Natl. Acad. Sci. USA, 71:3363-3366, 1974).

Animals

Biological UV-doses and the effect of an ozone layer depletion.

Effective UV-doses were calculated based on the integrated product of the biological action spectrum (the one proposed by IEC, which extends to 400 nm, was adopted) and the spectral irradiance. The calculations include absorption and scattering of UV-radiation in the atmosphere, both for normal ozone conditions as well as for a depleted ozone layer. For Scandinavian latitudes the effective annual UV-dose increases by approximately 4% per degrees of latitude towards the Equator. An ozone depletion of one percent increases the annual UV-dose by approximately 1% at 60 degrees N (increases slightly at lower latitudes). A large depletion of 50% over Scandinavia (60 degrees N) would give these countries an effective UV-dose similar to that obtained, with normal ozone conditions, at a latitude of 40 degrees N (California or the Mediterranean countries). The Antarctic ozone hole increases the annual UV-dose by 20 to 25% which is a similar increase as that attained by moving 5 to 6 degrees of latitude nearer the Equator. The annual UV-dose at higher latitudes is mainly determined by the summer values of ozone. Both the ozone values and the effective UV-doses vary from one year to another (within +/- 4%). No positive or negative trend is observed for Scandinavia from 1978 to 1988.

Ozone

Gonadotropin and ovarian steroid production in polycystic ovarian syndrome during suppression with a gonadotropin-releasing hormone agonist.

Six women with polycystic ovarian syndrome were treated with a gonadotropin-releasing hormone agonist prior to ovulation induction with gonadotropins. Buserelin nasal spray (600 micrograms/day) was given for 6 weeks. There was a gradual and significant decrease in the level of luteinizing hormone (LH) during the treatment period. No change was observed in the level of follicle-stimulating hormone. The estradiol, estrone, testosterone and androstenedione levels decreased significantly. No reduction was seen in the DHEAS level. After 4 weeks of treatment LH had reached postmenopausal levels, and testosterone and androstenedione were within the normal range. It is concluded that 4 weeks' treatment with 600 micrograms buserelin intranasally per day is sufficient to normalize the ovarian androgen production in polycystic ovarian syndrome prior to gonadotropin stimulation and to reduce the LH level avoiding premature luteinization or spontaneous LH surge.

Administration, Intranasal

Gonadotropin therapy of female infertility.

Anovulatory infertility in 134 women was treated with gonadotropins for a total of 318 cycles. The patients were classified into WHO group I, hypothalamic-pituitary failure (72 patients), and WHO group II, hypothalamic-pituitary dysfunction (62 patients). All patients in this group had failed to achieve pregnancy with clomiphene citrate therapy in repeated cycles. The pregnancy rate in group I was 72.2% vs 17.7% in group II. The 'take home' baby rate was 57.1% in group I vs 13.1% in group II. The rate of miscarriages was 14.3% without any significant difference between the groups. Multiple pregnancies occurred only in group I patients (19.2%). The conception rate was highest in the first four cycles, whereas no patient became pregnant after the sixth treatment cycle. Ovarian hyperstimulation syndrome occurred most frequently in group II patients, however, overall only 2.2% of the patients needed hospitalization because of hyperstimulation. Gonadotropin therapy must be considered an efficient and successful treatment of infertility in patients with hypothalamic-pituitary failure, whereas the success rate is rather poor in patients with hypothalamic-pituitary dysfunction.

Chorionic Gonadotropin

Gamete intrafallopian transfer (GIFT). The results of 93 consecutive treatments.

Eighty-two couples were treated with gamete intrafallopian transfer (GIFT) in 93 treatment cycles. Twenty-three clinical pregnancies resulted. Pregnancies were obtained in 40% of the cases where 5 or more ova were placed in the Fallopian tubes. In the cases where 4 or fewer ova were transferred, the pregnancy rate was 12%. Three miscarriages and one ectopic pregnancy occurred. Sixteen of the pregnancies were singleton, there were 5 twins, 1 triplet and 1 quadruplet. According to the present material, GIFT seems to represent a significant improvement in selected groups of patients.

Adult