Combined hormone therapy in postmenopausal women with features of metabolic syndrome. Results from a population-based study of Swedish women: Women's Health in the Lund Area study

OBJECTIVE: To delineate the influence of hormone therapy (HT) on features of metabolic syndrome with special reference to the composition and mode of administration of three specific HT regimens, all containing estradiol (E2) + norethisterone. DESIGN: The Women's Health in the Lund Area project screened all women (n = 10,766), born between 1935 and 1945. Complete data were obtained from 6,917 women. Those at or above defined cutoff limits were considered positively screened (n = 3,593) for metabolic syndrome. All of them were invited to undergo an oral glucose tolerance test; 2,923 women accepted. After excluding 200 women with impaired fasting glucose, 2,723 women were included in the present analysis. Serum lipids were determined by conventional standard methods at the department of clinical chemistry of Lund University Hospital. RESULTS: According to World Health Organization criteria, 2,123 women had normal glucose tolerance and 600 women had impaired glucose tolerance (IGT). IGT was less common (P = 0.001) among users of a transdermal patch [CYC-TRANS; E2 50 microg + norethisterone acetate (NETA) 250microg] compared with the two-combined oral regimen [CON-O (continuous oral E2 2 mg + NETA 1 mg) + CYC-O (sequential oral E2 2 mg + NETA 1 mg)]. Furthermore, IGT was more common among CON-O users when compared with either the CYC-O + CYC-TRANS group (P = 0.002) or the CYC-TRANS only group (P = 0.001). There were no significant differences between CYC-O versus CYC-TRANS or CON-O. Serum levels of total cholesterol were higher in the CYC-TRANS group than in the combined CON-O + CYC-O group (P < 0.05); they also were higher (P = 0.05) when comparing the CYC-O + CYC-TRANS versus CON-O as well as higher in CYC-TRANS versus CON-O (P < 0.05). Serum high-density lipoprotein cholesterol levels were higher in the CYC-O (P = 0.001), CYC-TRANS (P < 0.05), and the CYC-O + CYC-TRANS (P = 0.001) groups when compared with the CON-O users. There were no differences in the mean age, blood pressure (systolic and diastolic), body mass index, waste-hip ratio, or the rate of cigarette and alcohol consumption between the different hormone regimens. CONCLUSION: The risk of having a pathological glucose load was lower in transdermal versus oral users of HT. Transdermal HT could be regarded as first-line treatment in women at risk of developing diabetes.     

Permanent impairment of embryo development by hydrosalpinges

Recent reports suggest a deleterious effect of hydrosalpinges on pregnancy outcome for in-vitro fertilization (IVF) and improvement following surgical treatment. We compared the effect of hydrosalpinx on pregnancy outcome in 286 patients having 348 IVF cycles and followed the development of untransferred embryos for 7 days to determine if hydrosalpinges affect oocyte quality or embryo development. The delivery rate per retrieval was significantly lower for patients with hydrosalpinx, but was restored by surgical treatment to that of patients without hydrosalpinx. However, the implantation rate per embryo transferred and normal blastulation of untransferred embryos, which were significantly decreased in patients with hydrosalpinx, and growth arrest and degeneration of untransferred embryos, which were significantly increased compared to patients without hydrosalpinx, were not restored by surgical treatment of hydrosalpinges. We conclude that surgical treatment of hydrosalpinges decreases early pregnancy loss and improves pregnancy outcome, possibly by diminishing reversible deleterious effects exerted on the endometrium. As we have seen in our laboratory, hydrosalpinges may have a permanent negative influence on ovarian function, follicular development and oocyte quality since implantation of transferred embryos and normal blastulation of untransferred embryos remain low, and in-vitro growth arrest and degeneration remain high despite surgical treatment of hydrosalpinges.      

Effect of sunlight exposure on circulating 1,25-dihydroxyvitamin D in hemodialyzed patients and of exogenous parathyroid hormone in anephric patients

Sunshine exposure increased the serum concentration of 25-hydroxyvitamin D (25-OHD) in 9 hemodialyzed patients. Mean 1,25-dihydroxyvitamin D (1,25-(OH)2D) was unchanged, but in two patients with low initial 25-OHD values this increase was accompanied by a rise in circulating 1,25-(OH)2D, although not to normal levels. One hemodialyzed patient developed liver insufficiency with a resultant reduction of serum 25-OHD concentration accompanied by a decrease in serum 1,25-(OH)2D concentration. The results indicate that the circulating levels of 1,25-(OH)2D in patients with end-stage renal failure are to some extent regulated by the serum 25-OHD concentrations. Injection of parathyroid hormone (PTH) induced minor increases in serum concentrations of 1,25-(OH)2D in patients with end-stage renal failure and even in anephric patients, suggesting the existence of an extrarenal PTH-sensitive 1-alpha-hydroxylase. However, the enzyme was stimulated by supraphysiological concentrations of PTH, and therefore not necessarily of importance in the normal regulation of calcium metabolism.     

Efficacy of Amodiaquine in uncomplicated falciparum malaria in Nigeria in an area with high-level resistance to Chloroquine and Sulphadoxine/Pyrimethamine

Falciparum Malaria is hyperendemic in southern Nigeria and chloroquine resistance is an increasing problem. Therefore, the parasitological and haematological response to treatment with amodiaquine was studied in children under 5 years during a 14-day follow-up. Of 105 children who accomplished the study (out of 114 who were enrolled), 95.3% were parasite-negative on thick blood film on day 7, which decreased to 89.5% on day 14. The haemoglobin levels increased on average by 1.3% on day 14 (±1.9) and more pronounced in children with anaemia < 10 g/dl on enrolment. The number of patients with adverse events (mainly pruritus and nausea) was few. This study shows that amodiaquine is effective, safe and affordable in an area with high resistance to chloroquine.     

Radiation dose measurements with alanine/agarose gel and thin alanine films around a 192Ir brachytherapy source,using ESR spectroscopy

Alanine/agarose gel and alanine films in stacks have been used for measurements of absorbed dose around an HDR 192Ir source in a vaginal cylinder-applicator, with and without a 180 degrees tungsten shield. The gel and the films were analysed by means of ESR spectroscopy and calibrated against an ion chamber in a 4 MV photon beam to obtain absolute dose values. The gel serves as both dosimeter and phantom material, and the thin (130 microm) films are used to achieve an improved spatial resolution in the dose estimations. Experimental values were compared with Monte Carlo simulations using two different codes. Results from the measurements generally agree with the simulations to within 5%, for both the alanine/agarose gel and the alanine films.     

Comparison of the fertilizing capability of spermatozoa from ejaculates, epididymal aspirates and testicular biopsies using intracytoplasmic sperm injection

A prospective study was carried out to compare the fertilizing capability and pregnancy outcome following intracytoplasmic sperm injection (ICSI) using spermatozoa obtained from ejaculates, or surgically from epididymis or seminiferous tubules. A total of 77 ICSI cycles (one per patient) was included. In all, 28 patients had severe oligoasthenoteratozoospermia, 19 patients had obstructive azoospermia and 30 patients had non-obstructive azoospermia. The main outcome measures were fertilization rate per injected metaphase II oocyte and the clinical pregnancy rate per embryo transferred back to the female recipients. In patients with severe oligoasthenoteratozoospermia, the fertilization and pregnancy rates were 79 and 25 %. In patients with obstructive azoospermia, for whom epididymal spermatozoa were used, these were 75 and 28%, and in the non-obstructive group for which testicular spermatozoa were used for injection, they were 69 and 21% respectively. These rates were not significantly different in the three groups (P = 0.85 and P = 0.14 respectively), suggesting that spermatozoa from the ejaculates and epididymal or testicular biopsies are able to fertilize equally by using ICSI. Live birth per embryo transfer was significantly reduced in patients with non-obstructive azoospermia compared to the other two groups. The high abortion rate (50%) in the group in which testicular spermatozoa were used raises doubts about the developmental competence of such embryos.      

Influence of age and cell number of a tissue culture on its susceptibility to poliovirus

Summary By means of comparative virus titrations it is shown that significantly different titers may be found as a result of experimentally produced variations in the cultures used for titrations. The results were obtained by following the cytopathic changes daily in the microscope. The applied variations concerned the following factors: Age of the cultures used, time for last fluid change before virus inoculation and cell number of cultures of same age.Supported by a grant from the Swedish Association against Polio.     

Development of dopamine innervation and turning behavior in dopamine-depleted infant rats receiving unilateral nigral transplants

Three-day-old rats were bilaterally dopamine-depleted with 6-hydroxydopamine and 3 days later cell suspensions derived from the dopamine-rich ventral mesencephalic area were injected into the right rostral striatum. The transplants rapidly developed a substantial innervation of one striatum, so that by 15 days after transplantation (21 days of age) animals rotated away from the reinnervated side in response to amphetamine. The amount of turning correlated with the extent of innervation of the striatum as determined by tyrosine hydroxylase immunocytochemistry. By 25 days post-transplantation (31 days of age), animals turned in response to stress as well as amphetamine, although this later-developing phenomenon was not associated with any significant change in the extent of dopamine innervation.

A second group of animals was bilaterally dopamine-depleted at 3 days of age, but transplantation with nigral cell suspensions was delayed until maturity. Partial reinnervation of the rostral striatum occurred with this delayed transplant paradigm, and turning to both amphetamine and stress commenced at 15 days post-transplantation. In contrast to animals receiving transplants shortly after lesioning, these animals began to turn spontaneously at about 20 days post-transplantation. The serotonin hyper-innervation that occurs following dopamine depletion in infancy was not altered by dopamine transplants made at either time.

Results from both groups of transplant animals suggest that dopamine-rich transplants can provide substantial innervation that exerts some functional control over the striatum. This occurs despite the fact that neonatally dopamine-depleted rats, unlike adult-lesioned animals, survive quite well in the absence of striatal dopamine. However, the degree of incorporation into existing circuitry, and the types of regulation that result, may vary considerably depending on the age at which the tissue is transplanted.