Arne Ljungqvist

Sympathetic Innervation of the Juxtaglomerular Cells of the Kidney

Combination of a histochemical fluorescence method for biogenic monoamines and staining of juxtaglomerular cell granules demonstrated sympathetic nerve terminals in the rat kidney in the walls of the parts of the juxtaglomerular arterioles that contain granulated cells. This forms a morphological basis for a direct influence of sympathetic nervous activity on the liberation of renin. The juxtaglomerular granules were nonfluorescent, an indication that, in the rat, the granulated juxtaglomerular cells are not equivalent to mast cells.

Gender Verification in Competitive Sports

SummaryThe possibility that men might masquerade as women and be unfair competitors in women’s sports is accepted as outrageous by athletes and the public alike. Since the 1930s, media reports have fuelled claims that individuals who once competed as female athletes subsequently appeared to be men. In most of these cases there was probably ambiguity of the external genitalia, possibly as a result of male pseudohermaphroditism. Nonetheless, beginning at the Rome Olympic Games in 1960, the International Amateur Athletics Federation (IAAF) began establishing rules of eli-gibility for women athletes.Initially, physical examination was used as a method for gender verification, but this plan was widely resented. Thus, sex chromatin testing (buccal smear) was introduced at the Mexico City Olympic Games in 1968. The principle was that genetic females (46,XX) show a single X-chromatic mass, whereas males (46,XY) do not. Unfortunately, sex chromatin analysis fell out of common diagnostic use by geneticists shortly after the International Olympic Committee (IOC) began its implementation for gender verification. The lack of laboratories routinely performing the test aggravated the problem of errors in interpretation by inexperienced workers, yielding false-positive and false-negative results. However, an even greater problem is that there exist phenotypic females with male sex chromatin patterns (e.g. androgen insensitivity, XY gonadal dysgenesis). These individuals have no athletic advantage as a result of their congenital abnormality and reasonably should not be excluded from competition. That is, only the chromosomal (genetic) sex is analysed by sex chromatin testing, not the anatomical or psychosocial status. For all the above reasons sex chromatin testing unfairly excludes many athletes. Although the IOC offered follow-up physical examinations that could have restored eligibility for those ’failing’ sex chromatin tests, most affected athletes seemed to prefer to ’retire’. All these problems remain with the current laboratory based gender verification test, polymerase chain reaction based testing of the SRY gene, the main candidate for male sex determination. Thus, this ’advance’ in fact still fails to address the fundamental inequities of laboratory based gender verification tests.The IAAF considered the issue in 1991 and 1992, and concluded that gender verification testing was not needed. This was thought to be especially true because of the current use of urine testing to exclude doping: voiding is observed by an official in order to verify that a sample from a given athlete has actually come from his or her urethra. That males could masquerade as females in these circumstances seems extraordinarily unlikely. Screening for gender is no longer undertaken at IAAF competitions.

Gender verification of female athletes.

The International Olympic Committee (IOC) officially mandated gender verification for female athletes beginning in 1968 and continuing through 1998. The rationale was to prevent masquerading males and women with “unfair, male-like” physical advantage from competing in female-only events. Visual observation and gynecological examination had been tried on a trial basis for two years at some competitions leading up to the 1968 Olympic Games, but these invasive and demeaning processes were jettisoned in favor of laboratory-based genetic tests. Sex chromatin and more recently DNA analyses for Y-specific male material were then required of all female athletes immediately preceding IOC-sanctioned sporting events, and many other international and national competitions following the IOC model. On-site gender verification has since been found to be highly discriminatory, and the cause of emotional trauma and social stigmatization for many females with problems of intersex who have been screened out from competition. Despite compelling evidence for the lack of scientific merit for chromosome-based screening for gender, as well as its functional and ethical inconsistencies, the IOC persisted in its policy for 30 years. The coauthors of this manuscript have worked with some success to rescind this policy through educating athletes and sports governors regarding the psychological and physical nature of sexual differentiation, and the inequities of genetic sex testing. In 1990, the International Amateur Athletics Federation (IAAF) called for abandonment of required genetic screening of women athletes, and by 1992 had adopted a fairer, medically justifiable model for preventing only male “impostors” in international track and field. At the recent recommendation of the IOC Athletes Commission, the Executive Board of the IOC has finally recognized the medical and functional inconsistencies and undue costs of chromosome-based methods. In 1999, the IOC ratified the abandonment of on-site genetic screening of females at the next Olympic Games in Australia. This article reviews the history and rationales for fairness in female-only sports that have led to the rise and fall of on-site, chromosome-based gender verification at international sporting events.

Essay: Gender verification of female athletes

Genetic-based laboratory testing of female athletes who compete in women-only events was instituted in the late 1960s to replace the degrading alternatives of having to parade nude before panels of judges or endure close genital inspection. Testing seemed both appropriate and fair in a cold-war era during which the sex of some successful female athletes was being questioned, and the buccal smear—then a fairly new cytological test that depends on condensation of one of two X chromosomes—was not terribly difficult to administer. Those who proposed the idea could not have foreseen the consequences or the subsequent explosion in numbers of women athletes that would ensue over the next 30 years. Undoubtedly, the increasing popularity of women’s sports contributed to the desire to maintain a level playing field, as was described in 1972 by Eduardo Hay, a member of the International Olympic Committee’s Medical Commission. Procedures were, therefore, defined that included full clinical assessment of female athletes detected without two X chromosomes who wanted to continue to compete. Most, however, preferred either to feign injury or to retire than to subject themselves to the inevitable publicity and public scrutiny. A shame, since, as pointed out by Finnish geneticist Albert de la Chapelle in 1986, buccal smears were technically unreliable and detected athletes with genetic disorders, such as androgen insensitivity syndrome and gonadal dysgenesis, who were undeniably female. Paradoxically, the test would have permitted men with Klinefelter’s syndrome or XX males, who have a portion of the testicular determining gene (SRY) transposed onto the X chromosome, to compete.

Thrombin-inhibitory capacity of the injured vessel wall

The present study examined the appearance of thrombin activity in vitro after single and repeated in vivo balloon injury of the rabbit aorta. The in vitro ability of the injured vessel wall to bind and subsequently inhibit thrombin in the presence of defibrinogenated plasma was also assessed. Thrombin activity was assayed by measuring the levels of fibrinopeptide A generated in the presence of fibrinogen. These findings were correlated with the changes observed in light and electron microscopy. Thrombin activity on the vessel wall was increased five minutes and three hours after the initial and the repeated injury, and returned to control values one week after the initial injury. When the inhibition of thrombin was assayed in the presence of defibrinogenated plasma, a diminished inhibition capacity was observed after the repeated injury, which correlated with deposition of fibrin and an enhanced inflammatory reaction as measured by the density of granulocytes covering the injured neointima. Decreased thrombin inhibitory capacity of the injured neointima appears to be linked with its increased thrombogenicity.

Vein graft surgery in defibrase(R)-Defibrinogenated dogs

Abstract Dacron grafts were inserted into the inferior vena cava of the dog. One group (4 animals) were kept defibrinogenated for seven days by daily intravenous injections of Defibrase R starting 24 hours after surgery, a second group (6 animals) for seven days from the time of surgery and a third group (9 animals) for 10 days or 3 weeks commencing 2 days prior to surgery. The fibrinogen content in plasma during the period of defibrinogenation treatment was lowered to unmeasurable or very low values. The platelet count stayed normal. The four animals in the first group had thrombosed grafts at the start of defibrinogenation and three of them still had thrombosed grafts on the seventh day and one had a partially thrombosed graft. Out of the six animals operated upon at the start of defibrinogenation treatment four died due to haemorrhage within 24 hours. All grafts were patent. Out of nine animals operated upon in an already defibrinogenated state none died of haemorrhage. All grafts were patent at the end of defibrinogenation period and 3 out of 4 were still patent three weeks later.

Essay: Transsexual athletes—when is competition fair?

With the elimination of genetic-based testing to verify gender there remains no controversy with respect to athletic competition by phenotypic females with Y chromosomal material, or by individuals who have undergone prepubertal gender reassignment. The former are generally individuals with androgen insensitivity syndrome, whereas the latter comprise cases of sexual ambiguity caused by various rare genetic defects. In neither group can exposure to male sex hormones be argued to have any competitive advantage. Sports authorities are now attempting to establish when and if individuals who have undergone postpubertal gender reassignment, predominantly male-to-female transsexuals and often with legal recognition, can compete in their reassigned gender. Although there have been anecdotal reports of prominent athletes with proven or suspected genetic intersex disorders, only recently have some transsexual athletes begun to compete successfully in national and international events and many others are presumed to compete at lower levels. Perhaps the most famous of these is Renee Richards, nee Richard Raskin, a physician and competitive amateur tennis player who underwent sex conversion at age 41 years. Richards successfully sued the US Tennis Association to compete in the 1977 US Open Tennis Championships. She subsequently had a modestly successful tennis career— predominantly in women’s doubles—and on one occasion reached the finals of the US Open. In 1990, when the question of postpubertal transgendered athletes was first considered at the Workshop on Methods of Femininity Verification convened by the International Association of Athletic Federations (IAAF) in Monaco, the issue was discussed only in passing with a recommendation that the relevant sports authority assess individuals on a case-by-case basis. Adopted by the IAAF and the International Olympic Committee, this recommendation provided a framework for the next 15 years. With increasing recognition of gender dysphoria as a specific diagnosis, adoption of protocols for treatment via surgery and hormonal therapy, and an increasing number of transsexual athletes seeking to compete, however, the International Olympic Committee’s Medical Commission sought further opinion.

On fibrin distribution in organs of dogs during defibrination with the thrombin-like enzyme from bothrops atrox

Abstract The purified thrombin-like enzyme from the venom of Bothrops atrox, DefibraseR, has been injected intravenously to dogs in order to produce defibrination. The dogs were killed 1 2 – 6 hours after the injections and sections from lung, liver, kidney, spleen and muscle were examined by means of immunofluorescent and autoradiographic techniques. No occlusive vascular thrombi leading to organ infarctions were observed. Lung capillaries were sometimes found to contain small fibrin deposits 1 2 – 1 hour after the Defibrase injection. Fibrin deposits produced during the defibrination did, however, not seem to interfere with the glomerular filtration rate as measured by clearance of endogenous creatinine. Minor amounts of fibrinogen related material were in some dogs also observed in the red pulp of the spleen and in the liver sinusoides. The role of the fibrinolytic system and of the reticulo-endothelial system in the removal of fibrin during defibrination with Defibrase is discussed.

289 Sex and Gender in Sport: Fallacy of the “Level Playing Field”

There is controversy regarding participation in high profile competitive events by female athletes perceived as inappropriately “masculine” by competitors and others. Over 50 years, international sports bodies such as the International Olympic Committee (IOC) and the International Association of Athletics Federations (IAAF) employed - and ultimately discarded - various procedures to ensure feminiity. Though ostensibly to detect male imposters, in practice these identified women with genetic Disorders of Sex Development (DSD), such as androgen insensitivity syndrome, complete or partial; 5 alpha-reductase deficiency; mixed gonadal dysgenesis. Further, increased participation in womens sport has vastly enlarged the competitive field and the probability of athletes with a DSD competing. Do female athletes with a DSD have any “unfair” competitive advantage, especially since specific genetic endowment provides advantage to excel in specific events? This “endowment” can include recognized medical disorders such as height in Marfan Syndrome and delayed maturation and short stature in gonadal dysgenesis, even simple genetic variation such as more fast or slow twitch muscle fibers. A Finnish athlete with exceptional success in endurance Nordic skiing was found to have high hemoglobin and increased oxygen carrying capacity due to an inherited mutation in the erythropoietin receptor; similar mutations occur world wide. Even longer toes are associated with greater “lift-off” and success in sprint events. Thus the ideal of a “level playing field” is illusory and fundamentally women with some DSDs have no more competitive advantage than other elite athletes with favorable genetic characteristics.