Electroencephalography and magnetic resonance imaging after diving and decompression incidents: a controlled study.

Electroencephalography and magnetic resonance imaging after diving and decompression incidents: a controlled study. Undersea Hyper Med 1999.; 26(2):61-65.--Diving incidents with symptoms of decompression sickness (DCS) and/or arterial gas emboli (AGE) might increase the degree of pathologic change in the electroencephalogram (EEG) or magnetic resonance imaging (MRI) of the supraspinal central nervous system (CNS). Diving itself, even without known symptoms of DCS and/or AGE, has been proposed to increase the number of CNS lesions using either EEG or MRI. In the first part of a two-part study we examined the effects of recompression treatment on EEG in decompression incidents in a group of sport and professional divers compared with a control group of healthy naval divers. In the second part we recorded brain MRI from three groups of volunteers: 1) divers who were treated for DCS in pressure chamber, 2) divers who had never had symptoms of DCS (and/or AGE), and 3) healthy normal controls who were not divers. Our results indicate that DCS increases the incidence of pathologic EEG recordings, whereas recompression treatment decreases them. The results of MRI do not verify evidence of increased numbers of CNS lesions in normal divers as compared to non-diving, healthy control subjects, whereas some of the divers treated for DCS in a pressure chamber had hyperintense lesions in brain white matter. None of them had any abnormalities in EEG, neurologic performance, or psychologic behavior. Both EEG and MRI are sensitive and non-specific methods for judging suspected evidence of brain lesions from diving or diving accidents.

Neuropsychologic and cardiovascular effects of clemastine fumarate under pressure.

Allergic rhinitis and mild respiratory infections have been widely accepted as temporary contraindications for fitness to dive. Nonetheless, several sport and professional divers use antihistamines to ease ear, nose, and throat (ENT) problems, especially for opening tubal ostium. Some divers know they are unfit to dive, but for a variety of reasons (e.g., money or short holiday) they try to clear their ears. Thus, the use of antihistaminic drugs (like clemastine fumarate) is common during diving. This double-blind, crossover study indicates that this special antihistamine does not increase the sedative effects of nitrogen narcosis, nor does it increase the level of cardiac arrhythmias. Liberal use of antihistamines while diving cannot be recommended because of possible complications connected with different preparations and the temporary limitations they impose on the diver.

Postmenopausal oestrogen replacement therapy with subcutaneous oestradiol implants.

Ten postmenopausal patients were treated by means of subcutaneous oestradiol-releasing silastic implants. Half of the patients received 3 implants, each containing 12 mg oestradiol valerate (E2V), while the other half received 4 implants, each containing 27 mg oestradiol benzoate (E2B). Progestogen was added to the treatment for 14 days, 6 weeks after implant insertion and every fourth week thereafter. Serum levels of oestrone (E1), oestradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were followed up. The effects on endometrial thickness, uterine volume and breast tissue were evaluated by ultrasound, mammography also being used for breast examination. The follow-up period was 24 weeks, but the implants were not removed until the climacteric symptoms reappeared. E1 and E2 levels remained higher and gonadotrophin levels lower than the pretreatment values during the 24-week follow-up period. Oestrogen effects were seen in both the uterus and the breasts. Both types of implant were effective in relieving climacteric symptoms. The mean time for symptom return was 10 months (range 6-18 months) in the E2V group and 8 months (range 4-12 months) in the E2B group. Our results indicate that nonbiodegradable controlled-release oestrogen implants offer a safe, effective, convenient and well-accepted alternative means of administering oestrogen replacement therapy.

IgG subclasses of pneumococcal antibodies--effect of allotype G2m(n).

Antibody responses to three pneumococcal polysaccharides (types 3, 14, and 18C) were analysed after vaccination with a 23-valent polysaccharide vaccine. Antibodies to all three polysaccharides could be detected before immunization. Clear cut IgG, IgA, and/or IgM antibody responses to the polysaccharides were seen in three-quarters of the vaccinees. IgG2 was the predominant and IgG1 the second most abundant subclass of anti-pneumococcal IgG antibodies both before and after the vaccination. The relative proportions of IgG2 and IgG1 antibodies exhibited a continuous variation from 1:0 to approximately 0:2. After vaccination, G2m(n)-positive homozygotes had about four times more IgG2 antibodies (anti-14 and anti-18C) than G2m(n)-negative vaccinees. Heterozygotes occupied an intermediate position. The same pattern was seen less clearly in type 3 antibodies after vaccination, and in all three antibodies before vaccination. The G2m(n) allotypes had no detectable effect on the levels of IgG1, IgG4, or IgM antibodies, and possibly a weak effect on IgG3 and IgA antibodies (G2m(n)-positive homozygotes responded strongly).

Post-heparin plasma hepatic lipase activity as predictor of high-density lipoprotein response to progestogen therapy: studies with cyproterone acetate.

Cyproterone acetate (CPA) was administered to 13 menstruating women from day 14 to day 27 of the cycle at a dose of 5 mg/day. Serum lipoprotein lipid levels and postheparin plasma lipase activity were determined on day 27 of the cycle before treatment and during two treatment cycles. No significant changes were observed in hepatic lipase activity or in very-low-density (VLDL) or low density lipoprotein (LDL) concentrations. However, analysis of high-density-lipoprotein (HDL) subfractions by precipitation demonstrated a significant reduction in HDL2 cholesterol (-24%, P less than 0.05) during cyproterone acetate treatment. It is suggested that this change is related to oestrogen deficiency induced by inhibition of luteinizing hormone (LH) secretion.

Isotype concentrations of human antibodies to group A meningococcal polysaccharide.

Antibodies to meningococcal group A polysaccharide (MenA) in the sera of 34 vaccinated adults were quantitated by an isotype-resolving solid-phase RIA (IgA, IgM, IgG1, IgG2, IgG3, and IgG4). All individuals had antibodies before vaccination. The geometric mean concentration was 2.9 micrograms/ml. Two weeks after vaccination the mean antibody concentration had trebled. Average proportions of the three isotypes were then as follows: IgA 15%, IgM 48%, IgG 37%. No differences were found between individuals who had been immunized with the polysaccharide 7 to 8 yr earlier and "primary responders." The subclass composition of IgG antibodies was determined in the 24 postvaccination samples with a definite IgG response (greater than 2-fold increase). IgG1 was the predominant subclass in antibodies of some sera and IgG2 in others, but the average proportions of both subclasses were nearly the same. IgG3 and IgG4 were only found in occasional sera, but when present, each subclass accounted for up to 6%. Although the ratio of kappa and lambda chains could not be determined, there was evidence to suggest that it was higher in anti-MenA antibodies than in antibodies to protein antigens.

Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2.

Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.

Effects of betamethasone and ritodrine on the fetal secretion of lung surfactant.

Beta-sympathomimetic drugs and glucocorticoid agents are given in preterm labor to prevent severe consequences of prematurity. It is unclear whether beta-sympathomimetics accelerate lung maturation, or whether they only tend to delay preterm delivery. We have evaluated the effects of betamethasone and ritodrine in rabbits on alveolar lavage phospholipids in premature rabbits, a mean of 28.7 days from conception. Betamethasone given to 26-day-old fetuses increased the surfactant phospholipids, phosphatidylinositol and disaturated phosphatidylcholine; increased disaturated phosphatidylcholine/sphingomyelin ratio, and phosphatidylinositol (percent of phospholipids), as compared to untreated littermates, or to saline treated controls. A low dose of ritodrine given to the pregnant doe, and a high dose given at premature birth had no detectable effects on alveolar lavage phospholipids. However, a high dose of ritodrine given one day before the delivery to the fetus and at premature birth decreased the disaturated phosphatidylcholine/sphingomyelin ratio and phosphatidylinositol in alveolar lavage. While glucocorticoid administration increases the synthesis and secretion of surfactant phospholipids, a high dose of a betasympathomimetic drug may decrease the surfactant. However, spontaneous premature labor is associated with accelerated lung maturation, and accordingly the present results do not contradict the use of a low dosage of betasympathomimetic drug to delay preterm delivery.

High density lipoprotein-2 and hepatic lipase: reciprocal changes produced by estrogen and norgestrel.

The concentrations of plasma high density lipoprotein (HDL) and its subfraction HDL2 are influenced by endogenous and exogenous sex hormones. The catabolism of HDL2 is mediated by a lipolytic enzyme, hepatic lipase, which is present in endothelial cells covering the liver sinusoids. Since the activity of this enzyme is also regulated by gonadal and anabolic steroids, we examined whether the effect of sex steroids on plasma HDL is related to changes in hepatic lipase. In postmenopausal women, estradiol valerate (2 mg/day, orally) increased the HDL2 cholesterol and phospholipid concentrations by 20% (P less than 0.05). Simultaneously, the hepatic lipase activity of postheparin plasma decreased by 25% (P less than 0.05). The addition of levonorgestrel (250 micrograms/day, orally) to the treatment reversed both effects of estrogen, so that HDL2 cholesterol and phospholipid levels fell below and hepatic lipase activity rose above the respective pretreatment values. The hormones did not influence the HDL3 lipid concentrations or the lipoprotein lipase and lecithin:cholesterol acyltransferase activities. The results are compatible with the hypothesis that the effects of sex steroids on plasma HDL (HDL2) are mediated by changes in hepatic lipase activity.

Effects of oestradiol and levonorgestrel on lipoprotein lipids and postheparin plasma lipase activities in normolipoproteinaemic women.

The effects of oestradiol and levonorgestrel on plasma lipoprotein cholesterol (Chol) and triglyceride (Tg) levels and on postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activity were studied in 52 normolipoproteinaemic women. The androgen-derived progestin levonorgestrel increased postheparin plasma hepatic lipase (PH-HL) activity and decreased plasma high-density lipoprotein (HDL) lipid concentrations in a manner opposite to that of oestradiol. The relationships between PH-HL activity and HDL lipids suggest an important role for this enzyme as a mediator of sex hormone action on HDL.

Different effects of two progestins on plasma high density lipoprotein (HDL2) and postheparin plasma hepatic lipase activity.

Two progestins with different androgenic activity were compared for their effects on plasma high density lipoproteins and postheparin plasma lipase activities in premenopausal women. Levonorgestrel, a nortestosterone-derived steroid with androgenic activity reduced plasma HDL cholesterol by 17% (P less than 0.05) and HDL2 cholesterol by 30% (P less than 0.05), without changing the HDL3 cholesterol concentration. At the same time the postheparin plasma hepatic lipase activity was increased by 56% (P less than 0.01) whereas the lipoprotein lipase was not changed. None of these effects was reproduced during administration of medroxyprogesterone acetate, a progestin with low androgenic activity. The results suggest, first, that the decrease of HDL cholesterol observed during treatment with progestins is related to the androgenic activity of the steroid used, and, second, that the change in HDL (HDL2) is caused by androgen-induced increase of hepatic lipase activity.

Reduction of plasma high-density lipoprotein cholesterol and increase of postheparin plasma hepatic lipase activity during progestin treatment.

Twenty-seven menopausal women were given the synthetic progestin levonorgestrel for two weeks. The mean plasma high-density lipoprotein (HDL) cholesterol concentration decreased from 1.32 mmol/l to 1.01 mmol/l (p less than 0.001) during treatment. This was due to the selective reduction in plasma HDL2 cholesterol from 0.73 mmol/l to 0.44 mmol/l, whereas the plasma HDL3 cholesterol was not changed. The mean hepatic lipase (HL) activity of postheparin plasma increased from 20.6 to 35.3 mumol.h-1.ml-1 (p less than 0.001) while the lipoprotein lipase (LPL) activity was not changed. A significant inverse correlation existed between the HDL2 cholesterol concentration and HL activity both before (r=-0.49, p less than 0.01) and after (r=-0.39, p less than 0.05) treatment, and a significant correlation was observed between the changes in these two variables (r=0.39, p less than 0.05). These results are compatible with the hypothesis that HL participates in the regulation of plasma HDL2 levels and they suggest that progestin treatment reduces plasma HDL2 cholesterol concentration by increasing the hepatic lipase activity. It is not known whether this type of HDL2 reduction is accompanied by increased atherogenesis but as long as the issue is unresolved some caution is needed in the long-term use of levonorgestrel, particularly in women who simultaneously are given some other drug depressing plasma HDL2 concentration.

An oestrone-releasing vaginal ring in the treatment of climacteric women.

Post-menopausal patients were treated with a new form of oestrogen administration by using two types of oestrone-containing vaginal rings. It was observed that oestrone was absorbed from the vagina as demonstrated by elevated plasma concentrations of oestrone (E1) and oestradiol (E2). In 3 out of 4 patients the ratio of E1/E2 was 4-5 in the first plasma samples collected after the initiation of the treatment. After the first week of treatment this ratio had dropped to 0.8-1.5, which indicates an increase and stabilization in the conversion of oestrone to oestradiol within 1 wk of treatment. The high levels of plasma oestrogens were associated with a decrease of plasma gonadotrophins and the disappearance of climacteric symptoms. The first type of ring tested resulted in a high initial burst of oestrone release, as evidenced by high concentrations of oestrone and oestradiol during the first 2 wk. In the second type of vaginal ring the high initial oestrone release was not present and the plasma oestrone and oestradiol levels were stable. The patients tolerated the treatment well, and after gaining experience, easily accepted this route of self-administration. It seems that the vaginal silastic ring is an effective steroid-delivery system in post-menopausal women. As judged by plasma oestrone and oestradiol profiles, it seems that the second type of ring was preferable to the first one as an intravaginal releasing device.

Steroid and gonadotropin profiles in menopausal women on three different oral replacement regimens.

Three different estrogen-progestin regimens were studied in the treatment of menopausal symptoms. Plasma steroid and gonadotropin profiles were determined. As judged by the increase of plasma FSH concentrations, as well as by the decrease of plasma estrone and estradiol concentrations, one treatment-free week during a four week cycle was too long. This FSH increase could not even be eliminated by administering estrogen at half the treatment dose.