[What part did the Order societies play during the 18th century for the establishment of the Karolinska Institute?]. / Vilken roll hade frihetstidens ordensliv för tillkomsten av Karolinska institutet?

Sweden lost its military and political powers at the treaties after the wars of Charles XII. This was hard to accept by the ruling parties. They felt they were in the right to restore Sweden's dominance in Northern Europe. Poor finances could be compensated for by foreign subsidies at a reasonable political price. To compensate for lost ships and lost military equipment took time. However, new soldiers could only be replaced by the natural way and thus a full regeneration period was necessary to fill the soldier's cottages with new material. So, Sweden felt competent to engage in war activities now and then, in 1741, 1757, 1788 and 1809, with more or less disastrous results, however. The necessity of appropriate medical backup for war actions was not much acknowledged by the war enthusiasts. However, these wars now took place much closer to Sweden's own territory than before, or even within its borders. In contrast to the wars of the 17th and early 18th centuries, where victims were lost on foreign ground and war invalids had major difficulties to return home, the Swedish society was now much more confronted with the consequences of insufficient war medical services. During the 18th century a number of order societies based on philanthropy were established in Sweden. Among them the Order of Carpenters (Timmermansorden), which was founded in 1761, directed its services to aid invalids of house-building and of war. That war invalids were especially mentioned was probably due to the fact that the Order was founded under influence from experiences made during the Seven Years War, in which Sweden took part in 1757-61. In 1796 the Order had the resources to found a hospital, mainly for the benefit of war invalids. This hospital happened to be the only institution of this kind in whole Sweden until 1818, with the exception of an invalid corps i Carlshamn. This hospital obtained royal acknowledgement, and a All Saints' Day collect was allowed to be taken in the churches of Stockholm for the support of the hospital from 1798, the right existed for almost a hundred years. From the very beginning prominent surgeons and physicians in Stockholm became members of this Order of Carpenters and a majority of those who founded the Swedish Society of Medicine and its predecessors were also members. Very probably they took impression from the type of philanthropy the Order represented, which influenced their professional work in society. This is evidenced by a document in the archives of the Order of Carpenters, written in 1811 by E.C. Trafvenfelt, who was the principal founder of the Swedish Society of Medicine and who in 1809 suggested the Swedish Parliament to establish an institute for the education of surgeons, later called the Karolinska institutet.

Derivatives of 2-nitrofluorene cause changes of human sperm motility.

The effects on human sperm motility characteristics of 2-nitrofluorene and selected derivatives were studied in vitro, using computer aided sperm analysis (Cellsoft). Substances to be tested were dissolved in acetone and added to separated spermatozoa in culture media to final concentrations of 100 and 1000 microM. Aliquots were removed immediately (< 5 min.) and 24 hr after the addition and tested for sperm motility characteristics. Four of the substances tested; 2,4,7-trinitrofluoren-9-one (2,4,7-tNFO), 2,5-diaminofluorene (2,5-dAF), 7-hydroxy-2-nitrofluorene (7-OH-NF) and 2,7-diaminofluorene (2,7-dAF) showed strong detrimental effects on the sperm motility. Slight detrimental effects were also recorded using 2-nitrofluorene and 2,5-dinitrofluorene (2,5-dNF). Weak stimulatory effects were obtained using 2-acetoamidofluorene (AAF) and 2,7-dinitrofluorene (2,7-dNF). No significant effects were seen with 5-hydroxy-2-nitrofluorene (5-OH-NF), 2-aminofluorene (AF), 2-aminofluoren-9-one (AFO), 2-amino-9-hydroxyfluorene (9-OH-AF) or 9-hydroxy-2-nitrofluorene (9-OH-NF). The mechanism behind this effect is not known but it could be speculated that these lipophilic substances interact with the membranes or the cellular respiration.

Human sperm motility is affected by plasticizers and diesel particle extracts.

In order to test various drugs and possibly hazardous compounds on living cells in vitro a system with human spermatozoa was employed. A population of human spermatozoa was transferred into a defined medium by a swim-up procedure or by separation on a Percoll gradient. Such a population is rather homogenous with respect to motility characteristics and was found to be useful for this purpose. Different modes of response were recorded, indicating various effect mechanisms. Effects of various phthalates used as plastic softeners in the production of medical equipment, and extracts from diesel particulate material were recorded. All these compounds interfered with sperm motility in a dose-response fashion. Immediate effects of phthalates were modest, but upon prolonged exposure effects became more evident. Sperm motility was more affected by diethyl-hexyl and dibutyl phthalates. Significant effects were noted for the different phthalates with regard both to percent motility and to some of the various qualities of motility, such as velocity, linearity and amplitude of the track. Thus, the pattern of response considering the motion variables was not the same with the different phthalates. With regard to the effects on sperm motion di-n-octyl phthalate seemed to be the least toxic, followed by dibutyl phthalate. The initial effects of diesel particulate extracts were moderate and mainly restricted to percent motile sperm but upon exposure for 18 hr the effects became more pronounced for all the movement variables.

Smoking and reproduction. Short and long term effects and benefits of smoking cessation.

There have been many attempts during the last years to restrict smoking because of the significant health hazards. In particular the high prevalence of smoking among women in their reproductive years has been a matter of concern. This review was prompted in order to make the medical profession, and gynecologists in particular, confident with the underlying data. This will hopefully result in enabling them to provide balanced information to their patients, not overemphasizing the dangers of smoking, but rather presenting ways to properly recognize and treat tobacco dependence. It is a widely held view that the various risks imposed by smoking are very modest. A doubling of the risk for a rare problem may not prevent many women from continuing to smoke. However, a doubling of the risk for early miscarriage or a significant reduction of success rate in the treatment of infertility may be much more discouraging. The purpose of this review is to list the various effects smoking may have on the different phases of reproduction and to present an overview of the explanation models which have been suggested. Late effects on the child and its development will also be discussed. Hopefully, this will lead to proper concern about the problems and thus increase the motivation to quit smoking even before attempting a pregnancy. In addition, we give some hints on smoking cessation programs.

Could bacterial vaginosis be due to the competitive suppression of lactobacilli by aerobic microorganisms?

Bacterial vaginosis (BV) is characterized by lack of lactobacilli and predominance of anaerobic species. Ciprofloxacin is active against a great number of aerobic bacteria. The effect of ciprofloxacin on the vaginal microbial flora was studied both in healthy subjects and in patients with BV in order to test if BV may be due to competitive suppression of lactobacilli by aerobic species. About half of the patients were relieved of their symptoms. No adverse effects on the microbial profile or colonization by lactobacilli were produced by the drug. Lactobacilli known to be able to produce hydrogen peroxide were found to be significantly more common in healthy women than in women with BV. The species most frequently related to vaginal health were Lactobacillus jensenii and Lactobacillus rogosae.

Sperm count and motility influence the results of human fertilization in vitro.

In order to select sperm characteristics that can predict the outcome of in-vitro fertilization-embryo transfer (IVF-ET), semen samples delivered in conjunction with this treatment were studied carefully. We have analysed these data retrospectively in relation to the outcome of treatment. Ninety-one couples were treated for tubal infertility by IVF-ET. Fifteen women became pregnant. Sperm were isolated from semen using a swim-up technique and in most cases 40-80 x 10(3) (range 20-120 x 10(3)) motile sperm per ovum were used for insemination. The couples were divided into three groups: group A who achieved pregnancies, group B who achieved cleaved ova but no pregnancies, and group C who achieved no ova that were cleaved 48 h after oocyte recovery. Comparisons between these groups showed that some characteristics of the native semen samples and the swim-up preparations were significantly different: the sperm concentration (P = 0.001) and total sperm count (P = 0.003) in the native sample, the number of sperm recovered during 30 min of swim-up (P = 0.001), and the specific progressive motility of sperm in the swim-up preparation, both at the time of insemination and on each day, up to 5 days thereafter (P = 0.002-0.028). No pregnancy was achieved with a sperm concentration below 26 x 10(6) ml-1 in the native sample. Some of the sperm characteristics studied in this paper may be of value in the pretreatment evaluation for IVF treatment.

Comparison between a conventional index of progressive sperm motility and movement variables analysed by CellSoft.

Two different techniques of human sperm motion analysis were compared. In 25 ejaculates, diluted to an appropriate concentration, the sperm motion index called "specific progressive motility" (SPM) was assessed by a modified conventional method. The same sperm preparations were also analysed by the CellSoft system for computer assisted sperm analysis (CASA). The SPM-value was found to correspond mainly to the variables motility and curvilinear velocity presented by CASA (multiple r = 0.92, P less than 0.001). Linearity of sperm progression, lateral head displacement, and beat cross frequency did not significantly contribute to the relationship between SPM and CASA. For comparative studies between SPM and CASA the logarithmic values of SPM are recommended.

Changes in human sperm chromatin stability during preparation for in-vitro fertilization.

This study was designed to define the effects of sperm preparation on sperm chromatin stability in relation to in-vitro fertilization (IVF). Semen samples used for IVF-embryo transfer (ET) in the treatment of infertility due to tubal factors were studied. Cases with semen variables below reference limits in previous samples were excluded. Sperm were prepared by a swim-up technique employing either of two different tissue culture media, Ham's F-10 or Earle's balanced salt solution. Sperm chromatin stability was tested by exposure both to sodium dodecyl sulphate (SDS) only and SDS together with a zinc-chelating agent, disodium ethylene diamine tetraacetate (SDS-EDTA). Sperm head swell scores were defined under different experimental conditions and the relationship to sperm motility, morphology, fertilization rate and pregnancy occurrence was tested. No differences were seen between the chromatin stability of sperm from the original sample and that after swim-up preparation, neither immediately after completion of the swim-up procedure, nor at the time of insemination of ova. With time, the chromatin became more stable, which occurred to a similar extent both in the original sample and in swim-up preparations using Ham's F-10. Otherwise, sperm chromatin stability was unaffected by either of the two media used for swim-up. At higher incubation temperatures, decondensation in SDS was enhanced. Altogether, no correlation was found between sperm chromatin stability or enhancement of decondensation by temperature and the success of IVF treatment expressed in fertilization rates or pregnancies. The results are reassuring in that only small changes in sperm chromatin stability occurred during the preparation for IVF. As long as semen of presumably good quality is used, these changes in chromatin stability do not seem to be of clinical importance.

Morphology of seminal and swim-up spermatozoa and the outcome of in vitro fertilization and embryo transfer.

Tubal infertility was treated by in vitro fertilization-embryo transfer (IVF-ET) in 112 couples. Twenty-eight pregnancies were obtained in 140 treatment cycles. Couples are accepted for treatment in our IVF-ET programme if previous semen samples fulfil the inclusion criteria: ejaculate volume greater than 1.5 ml, concentration of spermatozoa greater than 15 x 10(6) ml-1, greater than 40% motile spermatozoa, and greater than 25% spermatozoa with normal morphology. In order to determine to which extent IVF-ET treatment results are influenced by sperm morphology, within this selected group of patients, we have retrospectively analysed the data from both original semen samples and swim-up preparations. The sperm morphology was not related to the outcome of treatment in terms of fertilization (ovum cleavage rate), early embryo development, or pregnancy. Nor was any relationship detected between early embryo development or pregnancy and the degree of improvement in morphology resulting from the swim-up procedure. However, if improvement in morphology by swim-up was high, ovum cleavage rate was low. Sperm morphology within the limits set by our inclusion criteria could not predict the outcome of IVF-ET treatment. It is further concluded that the presence of abnormal spermatozoa at the site of fertilization may be without harm if only the number of normal sperms is high enough.

Effects of propranolol and caffeine on movement characteristics of human sperm.

Human sperm, separated on Percoll gradients and transferred to cell culture medium, were exposed to various concentrations of propranolol (0.8-800 microM) or caffeine (3 microM-17 mM) for 4 h. Their motility pattern was analysed after 5 min and 4 h, employing the computerized Cellsoft system. Curvilinear velocity (VCL), percentage motile sperm, linearity (LIN), mean amplitude of lateral head displacement (ALHMEAN) and beat cross-frequency (BCF) were assessed. Both drugs had a practically immediate effect on the sperm. Propranolol concentrations greater than 80 microM had a negative effect on all movement variables, except VCL and ALHMEAN, which showed a slight, non-significant, initial increase. LIN and the percentage motile sperm appeared to be somewhat negatively affected at lower concentrations (80 microM) than the other variables, and were reduced further at higher concentrations and with time. The presence of 800 microM propranolol immobilized all sperm within 4 h. Caffeine at 1.7 and 5 mM, increased VCL and ALHMEAN. In contrast, the highest caffeine concentration tested (17 mM) had a negative effect on all variables at 4 h after addition.

The early luteal phase in successful and unsuccessful implantation after IVF-ET.

The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate and human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non-pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity.

Serum factors stimulate the motility of human spermatozoa.

Motile human sperm were collected from a Percoll gradient and the effects on sperm motility of human serum, various serum fractions, follicular fluid and seminal plasma were assessed. In culture medium alone (RPMI-1640) sperm motility was lost after about 5 h. The addition of male blood serum both enhanced sperm motility and prolonged viability very significantly. Albumin, seminal plasma and follicular fluid all stimulated sperm motility but to a much lesser extent than did blood serum. No difference was noted between male serum or female serum which had been collected during the follicular or luteal phases of hormone-stimulated cycles and which contained high levels of oestradiol. Serum fractions obtained by separation on Sephacryl S-300 column were tested for their ability to enhance sperm motility. The most pronounced effect, much superior to that achieved by the albumin fraction, was obtained by a fraction with a molecular weight of around 200 kD. In conclusion, certain factors in human serum, which are different from albumin, strongly support sperm motility. The high serum concentrations of oestradiol resulting from hormone stimulation for in-vitro fertilization do not invalidate the use of serum from the same patient during sperm preparation, or in the medium used for ovum insemination and culture.