Conventional breeding programmes and genetic resistance to animal diseases.

The power of selection is illustrated by the increase in the average annual yield of dairy cows in Sweden in kg fat-corrected milk from 2,500 kg in the year 1900 to 8,200 kg in 1997. More than a half of this improvement has a genetic origin. The breeding goal for dairy cattle has successively been broadened to cover traits other than production. The prerequisites for a successful breeding programme and the consequences of the process are presented in this article. The dramatic improvement of the reproduction techniques and statistical tools for genetic evaluation of breeding stock and selection, which have occurred during the last 50 years, is also discussed. The factors which affect the genetic gain are described in detail to demonstrate the possibility of making genetic gains in traits reflecting disease resistance. The Swedish procedure of disease recording and the procedures for genetic evaluation of fitness traits, such as disease resistance and female fertility, are described. The existence and consequences of negative genetic correlations between production and fitness traits are dealt with, as is the procedure for multi-trait selection. An illustration of methods for performing multi-trait selection in real life, and the consequences of such selection in an envisaged Nordic selection scheme, are given. Finally, the authors review the present genetic trends for fitness traits of dairy cows in Sweden.

Treatment of premenstrual syndrome by spironolactone: a double-blind, placebo-controlled study.

BACKGROUND: To reevaluate whether spironolactone, a steroid receptor antagonist, is effective in improving premenstrual syndrome (PMS) in a double-blind, placebo-controlled cross over study. METHODS: Thirty-five women with PMS were given one tablet of 100 mg spironolactone or placebo daily from day 14 of the menstrual cycle until the first day of the following menstruation. Two pretreatment cycles were observed for diagnosis in each woman, followed by 6 treatment cycles with spironolactone and placebo applied in either the first or second 3 months. The assessment of symptoms and diagnosis of PMS were based on prospective daily self-ratings made by the women using a validated visual analogue scale. RESULTS: The treatment with spironolactone was associated with an improvement in PMS symptoms compared to placebo as judged by significant decrease in negative mood symptom scores (p < 0.001) and somatic symptom scores (p < 0.001). Of the individual symptoms, spironolactone significantly improved irritability, depression, feeling of swelling, breast tenderness and food craving in comparison to placebo. A lasting effect of spironolactone was observed in women started with spironolactone after cross over to placebo. CONCLUSIONS: Spironolactone appears to be an effective therapy for the negative mood changes and somatic symptoms in PMS.

Oral contraceptives in premenstrual syndrome: a randomized comparison of triphasic and monophasic preparations.

Thirty-seven women with cyclical mood changes, either only in the premenstrual phase ('pure PMS') or during the entire cycle with premenstrual aggravation ('PMA'), were recruited to participate in a randomized study investigating the effect of three different oral contraceptives (OCs) on mood symptoms; 32 out of the 37 women completed the study. The monophasic ethinylestradiol (EE)/desogestrel (DSG) OC was compared, in a single (doctor)-blind cross-over design, with a monophasic and a triphasic levonorgestrel (LNG)-containing combined OC. The women kept a record of their symptoms and complaints by noting daily ratings using a validated visual analogue scale. One pretreatment cycle was followed by four treatment cycles, two cycles on each OC. All OCs had a beneficial effect on the PMS symptoms compared to the pre-treatment period. There were no changes between consecutive cycles. Cyclical symptom changes were noted during all OC treatment. The monophasic desogestrel pill provoked less changes in mood parameters than the monophasic and triphasic levonorgestrel OCs. However, physical complaints were less frequently reported during the use of the triphasic preparation as compared to the monophasic desogestrel preparation. Women with 'pure' PMS (premenstrual syndrome) were more consistent in their reactions on OCs compared to women with PMA.

Influence of different levels of dietary casein on initiation of male rat liver carcinogenesis with a single dose of aflatoxin B1.

To analyze the influence of different levels of dietary casein on the initiation process, male Wistar rats, pair-fed on isocaloric diets containing 5, 15 or 40% casein were initiated with a single dose of aflatoxin B1, 28 days after the experimental start. From day 4 after initiation and until selection of initiated cells was started, 25 days later, rats were fed the 15% casein diet, providing an identical dietary background during the selection period. Promotion/selection of initiated cells was performed by the combined treatment with 0.02% 2-acetylaminofluorene in the 15% casein diet for 2 weeks and a two-thirds partial hepatectomy (PH) in the middle of this period. The number of enzyme-altered hepatic lesions per rat was shown to increase with increasing content of casein in the diet, both when liver sections were stained for gamma-glutamyltransferase and with immunohistochemical staining for the placental form of glutathione-S-transferase. Non-initiated rats fed the different levels of casein exhibited a very low number of foci. Livers were secured also from non-initiated rats at the same point of time as initiation was performed. Whereas no significant differences in the total microsomal content of cytochrome P450 were observed, a higher microsomal capacity to perform 16 alpha-hydroxylation of 4-androstene-3,17-dione was observed in preparations from rats fed 40% casein, when compared with rats receiving the 5% casein diet. The dietary protein content at the time of initiation did not affect the expression of the c-rasHa, c-myc or c-fos protooncogenes, either at initiation, on day 3, or at PH.

Relationship of fertility to milk yield in Swedish cattle.

Data consisted of 48,830 and 21,136 records of Swedish Red and White and Swedish Black and White cattle. Fertility in virgin heifers and in first lactation cows was measured by first service pregnancy rate and number of services per pregnancy. Production trait considered was FCM produced in first 100 d of lactation. The heritabilities for fertility traits in virgin heifers and first lactation cows were about .05 in both breeds. The genetic correlations between fertility measures within parity were close to one in both breeds, suggesting that these were measures of the same trait. The genetic correlations between fertility in virgin heifer and in first lactation were about .88 for Swedish Red and White breed and between .6 and .7 for Swedish Black and White breed. The association between fertility and production in first lactation cows was antagonistic, with genetic correlations between first service pregnancy rate and milk yield of -.13 and -.32 for Swedish Red and White and Swedish Black and White breed, respectively. The association between first service pregnancy rate in virgin heifers and milk yield in first lactation was also antagonistic, with genetic correlations of -.14 and -.41 for Swedish Red and White and Swedish Black and White breed, respectively.

Effects of neonatal and adult castration and of testosterone substitution in male rats on growth of enzyme-altered hepatic foci in the resistant hepatocyte model.

Marked sex differences in the growth of enzyme-altered hepatic foci have been observed in rats treated according to the "resistant hepatocyte model." The present study was performed to investigate the effect of neonatal and adult castration of male rats, with or without testosterone substitution, on the growth rate of foci during selection of initiated cells with 2-acetylaminofluorene and partial hepatectomy. Neonatal castration of male rats decreased focal growth to the same level as in female rats. Castration of adult male rats 2 wk before initiation with diethylnitrosamine also decreased the growth rate of foci, but less markedly than in neonatally castrated rats. Testosterone substitution of male rats castrated as neonates or as adults, from 10 days after initiation with diethylnitrosamine, restored focal growth to that of sham-castrated controls. Previous investigations concerning the role of gonadal hormones in sex differentiation of various liver functions indicated a role of the hypothalamo-pituitary-liver axis in mediating the effects of androgens. It is therefore also suggested that the effects of androgens on early steps of hepatocarcinogenesis observed in the present study are mediated by similar mechanisms, possibly through an influence on the metabolism of 2-acetylaminofluorene.

The influence of copper intrauterine device on fatty acid composition of cervical mucus lecithin.

Fatty acid composition of lecithin was analysed in midcycle cervical mucus obtained from 19 women using a copper intrauterine device (Cu-IUD) and 16 controls. In both groups, palmitic (16:0) acid was the predominant fatty acid and oleic (18:1) acid the second largest component. In women using a Cu-IUD, levels of myristic (14:0) acid were significantly lower, while levels of linoleic (18:2) and docosahexaenoic (22:6) acid were significantly higher than in controls. These changes in fatty acid composition could not be related to duration of IUD use and were very similar to those observed in women with primary unexplained infertility, suggesting that the Cu-IUD-induced modification of fatty acid pattern in midcycle mucus lecithin may be part of the contraceptive mechanism of action.

The contraceptive efficacy of a Cu-IUD: size of the device and the uterine cavity.

This investigation deals with a small Cu-7 IUD (Cu-7-P), originally designed for women with uterine cavities less than 7 cm in sound measures. The accidental pregnancy rate was almost doubled when this small IUD was used in women with normal-sized uterine cavities (sound measures 7-8 cm), when compared to that in women with small-sized uteri. It was assumed that this difference in efficacy might be at least partly caused by the distribution of the increased fibrinolytic activity of the endometrium in the 2 groups of women.

Investigation of the mechanism of perforation of an intrauterine device in pigs and dogs.

In the last few years the risk of perforations in connection with the insertion and later use of intrauterine devices (IUDs) has been the subject of much discussion in Sweden. In this experimental study, which was carried out on five pigs and nine dogs and in which four different types of IUDs were used, the following clinical situations encountered in women were simulated: IUD in correct position in the uterus, IUD in an adverse position in the uterus, and IUD more or less inserted through the uterine wall. The animals were observed for 3 to 6 months. The findings indicate that, when perforation occurs, it is most probably ascribable to the insertion procedure.

The possible risks of a copper and an inert intrauterine device situated in the abdominal cavity: an experimental study in pigs and dogs.

The possible injurious effects of abdominal intrauterine devices (IUDs), including Cu-IUDs, inert IUDs, and "closed' IUDs, were evaluated in an experimental study. Pigs and dogs were used as they have, respectively, a propensity to form adhesions and a pronounced tendency to develop serious peritonitis. The reactions expected in humans might be intermediate to those found in these two kinds of experimental animals. The results of this study indicate that an inert or copper-bearing IUD usually remains in its initial position in the abdominal cavity, encapsulated by adhesions. The risk of strangulation of the intestine by a "closed' IUD seems minimal.

Low risk of pelvic inflammatory disease in young never-pregnant women using Gravigard.

The present four-center investigation involves 516 never-pregnant women in whom a copper-7-intrauterine device (Cu-7-IUD) was inserted. Out of these patients 173 were teenagers at the time of insertion. A "small-sized" Cu-7-IUD (Cu-7-Nullip) - designed for nulliparous women - was randomely used instead of the commercially available Cu-7-IUD (GravigardR) in 76 - 44 of whom were teenagers - out of the 516 women. The incidence of pelvic inflammatory disease (PID) of 9,080 woman-months was reviewed. In the present study the incidence of PID varied from one center to another between 0.9 and 1.4 per cent/year in women wearing Cu-IUDs. When comparing these figures with the estimated incidence (1.2%) in the population of fertile-aged women, it was concluded that the risk for PID was not increased in never-pregnant women using Cu-IUDs, including teenagers as well as women of 20 years of age or more. No difference in the incidence of PID was observed between the GravigardR and the Cu-7 Nullip.

PIP: A prospective, 4-center study with special reference to the risk of pelvic inflammatory disease (PID) in young nulligravida who use copper 7 IUDs is reported. This series included 516 never-pregnant women who had a copper 7 device (Gravigard) inserted during the period 1971-1978. 173 of this group were aged 15-19 years at time of insertion. A small-sized copper 7 nullip was randomly inserted in 44 teen-aged women and in 32/243 women aged 20 years or more. PID had occurred in 11 (2.1%) of the 516 patients. In 3 of these cases the PID was caused by gonorrhea. During the 1st month after insertion of the copper IUD, additional cases of PID occurred. In 4/5 the genital infection was caused by gonorrhea and occurred in teen-aged patients. A nullip had been inserted in 1/4 of these patients. Incidence rate of PID of 9080 woman-months varied from center to center from .9-1.4%/year in women wearing copper IUDs. When comparing these figures with the estimated incidence (1.2%) in the population of fertile-aged women, the risk for PID was not increased in never-pregnant women using copper IUDs, including teen-agers as well as women 20 years or older. No difference in the incidence of PID was observed between the Gravigard and the Nullip devices.

Perforation of the uterus by the copper-t and copper-7 intrauterine contraceptive devices.

Uterine perforation in patients wearing the Copper-T and the Copper-7 intrauterine contraceptive devices has been studied. In Bollnäs, Sweden, three perforations occurred in 1 156 insertions of the Copper-7, and in New York, USA, six perforations occurred in 1 153 insertions of the Copper-T. Cervical perforation seems to be a special feature of the Copper-T, while the Copper-7 tends to perforate through the uterine wall. The perforations can be divided into "primary" perforations, related to the insertion procedure, and "secondary" perforations, caused by uterine contractions. The diagnosis and treatment of uterine perforations by intrauterine devices is discussed.

PIP: A study of uterine perforation by Copper-T and Copper-7 IUDs is described. 6 perforations out of 1153 insertions of the Copper-T at The New York Hospital-Cornell Medical Center in New York and 3 perforations out of 1156 insertions at the Bollnas Hospital in Sweden are described. This study indicates a high incidence of perforation. Design of the device has much to do with the risk of perforation. Risk seems to be less if the device conforms to the uterine cavity. Perforation is primary when related to the insertion procedure and secondary when caused by uterine contractions. The Copper-T tends to perforate the cervix and the Copper-7 tends to perforate the uterine wall. The diagnosis of uterine perforation with IUDs is difficult but important.