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Scrotal temperature is increased in disposable plastic lined nappies
Abstract
Male reproductive health has deteriorated in recent decades. It is proposed that increased testicular temperature in early childhood, due to the use of modern disposable plastic lined nappies (diapers), could be an important factor contributing to this decline.
Scrotal skin temperature was measured non-invasively in 48 healthy children aged 0-55 months (three age groups) for two 24 hour periods in randomised order (either cotton or disposable plastic lined nappies) using a portable, miniature recorder.
Mean 24 hour scrotal temperature (2880 measurements) was significantly higher in all age groups during the periods of plastic nappy use than with cotton nappies (p < 0.001). The rectoscrotal temperature difference was significantly higher with cotton than with plastic nappy use (p < 0.01).
Scrotal hypothermia is an important factor for normal spermatogenesis. This study shows that scrotal temperature, which closely reflects testicular temperature, is increased in boys wearing disposable plastic lined nappies. The physiological testicular cooling mechanism is blunted and often completely abolished during plastic nappy use. The present results establish the basis for further research on the impact of increased testicular temperature in infancy on later spermatogenesis.
... Scrotal hyperthermia is a welldocumented mechanism of abnormal spermatogenesis in common diseases associated with male infertility (e.g., varicocele and undescended testis) (7)(8)(9)(10)(11). Scrotal heat stress has also been linked to occupational exposure to high temperatures and certain lifestyle factors, including use of disposable plastic-lined diapers in children, prolonged car driving, heated car seats, daily activities, sedentary work, posture, and clothing (12)(13)(14)(15)(16)(17)(18). ...
... Higher testicular or scrotal temperature elevation between 1 C and 2.9 C was more consistently associated with a sustained and considerable negative effect on spermatogenesis and fertility (7,21,43,44). For that reason, a scrotal temperature increase of more than 1 C above baseline has been suggested as a possible minimal thermal gradient capable of inhibiting spermatogenesis (13,42). Therefore, maintaining scrotal temperature elevation within a 1 C margin can serve as a reasonable protective goal. ...
To evaluate methods of prevention of scrotal hyperthermia in laptop computer (LC) users.
Experimental study.
University hospital.
Twenty-nine healthy male volunteers.
Right and left scrotal temperature and LC and lap pad temperatures were recorded during three separate 60-minute sessions using a working LC in a laptop position: session 1, sitting with closely approximated legs; session 2, sitting with closely approximated legs with a lap pad below the working LC; and session 3, sitting with legs apart at a 70°angle with a lap pad below the working LC.
Scrotal temperature elevation.
Scrotal temperature increased significantly regardless of leg position or use of a lap pad. However, it was significantly lower in session 3 (1.41 °C ± 0.66 °C on the left and 1.47 °C ± 0.62 °C on the right) than in session 2 (2.18 °C ± 0.69 °C and 2.06 °C ± 0.72 °C) or session 1 (2.31 °C ± 0.96 °C and 2.56 °C ± 0.91 °C). A scrotal temperature elevation of 1 °C was reached at 11 minutes in session 1, 14 minutes in session 2, and 28 minutes in session 3.
Sitting position with closely approximated legs is the major cause of scrotal hyperthermia. Scrotal shielding with a lap pad does not protect from scrotal temperature elevation. Prevention of scrotal hyperthermia in LC users presently is not feasible. However, scrotal hyperthermia may be reduced by a modified sitting position (legs apart) and significantly shorter use of LC.
... I t has been hypothesised that the use of modern disposable, plastic lined nappies (diapers) could be an important factor in the increasing incidence of testicular cancer in adult age. 1 No information has been published about testicular cancer incidence in relation to such nappy use. ...
... This finding is in contradiction to the proposed hypothesis. 1 It should be noted, however, that only four mothers reported that their sons (two cases; two controls) used disposable nappies exclusively. All other boys who used disposable nappies used them in addition to other types of nappies. ...
Information on the use of disposable nappies in childhood was available for 296 testicular cancer cases and 287 population controls in Denmark. No association was found between disposable nappy use and the subsequent risk of testicular cancer in adulthood.
... Developmental stage-specific temperature control of testis development and function Indeed, the temperature of an undescended testis in its cryptorchid location in 13-to 180-month-old boys is significantly higher than that of the contralateral normally descended testicle (34.4°C ± 0.9 versus 33.2°C ± 1.2; p < 0.001) [8]. However, the scrotal temperature, which closely reflects the testicular temperature, is increased in boys wearing disposable plastic-lined nappies that blunt or even abolish the physiological testicular cooling mechanism without, however, affecting adult fertility [9]. Another phenomenon inconsistent with a negative effect of high temperature is associated with mutation of the SRD5A2 gene. ...
Spermatogenesis in mammals is a heat-sensitive developmental pathway incompatible with the typical mammalian body temperature of 37 °C. It is thought that this is the reason why the testicles of most mammalian males are outside of the body cavity, in the scrotum, where they function at approximately 33 °C. It has been suggested that the abnormally high temperature environment of cryptorchid testes may lead to impaired testicular development and adult infertility. Here, I summarize the clinical, genetic, and histological evidence that argues against temperature stress and in favor of hypogonadotropic hypogonadism as the underlying cause of adult infertility in cryptorchidism.
Patient summary: Infertility and an increased risk of testicular cancer in patients diagnosed with undescended testes are the consequence of a hormonal deficiency rather than temperature-induced cellular damage. Cryptorchidism therefore requires both surgical and hormonal treatment.
... In the other vain, one study shows (Partsch et al., 2000) that scrotal temperature, which closely reflects testicular temperature, is increased in boys wearing disposable plastic lined nappies. The physiological testicular cooling mechanism is blunted and often completely abolished during plastic nappy use. ...
L'impact des expositions de la vie courante, et en particulier de la température, sur la reproduction masculine est très étudié. Dans ce projet, nous avons étudié deux principaux paramètres liés à l'infertilité après une exposition testiculaire à une augmentation modérée de température (+2°C) chez des hommes sains : la morphologie et l'aneuploïdie du spermatozoïde et exploré leur potentielle réversibilité. Nous avons conçu un protocole expérimental qui a impliqué 5 hommes fertiles et une population témoin de 27 autres hommes fertiles. L'augmentation de température testiculaire et épididymaire a été obtenue en maintenant les testicules dans une position supra-scrotale au moyen de sous-vêtements spécialement conçu, portés 15 +/- 1heure par jour pendant 120 jours consécutifs. La première partie de ma thèse a été consacrée à l'étude de l'augmentation de température sur la morphologie des spermatozoïdes et l'indice des anomalies multiples (IAM). Nous avons observé un impact significatif sur la morphologie du sperme et l'IAM entre le 20ème et 34ème jour reflétant un effet sur les stades de spermiogenèse et de méiose. Cet effet drastique a été présent pendant toute la période de chauffage et la récupération des valeurs initiales a été observée au 73ème jour. Dans une deuxième partie, les aneuploïdies des chromosomes X,Y, 18 ont été analysées par hybridation in situ par la fluorescence (FISH) avant, pendant et après l'augmentation modérée de température. Nous avons constaté une augmentation significative de l'aneuploïdie totale du sperme, de la disomie sexuelle et de la nullisomie au 45ème jour après chauffage. Ces effets ont été complétement inversés après deux cycles de spermatogenèse après l'exposition à la chaleur. Ces résultats confirment l'impact de la température sur la spermatogenèse et peuvent avoir des implications cliniques dans l'infertilité masculine et notamment le concept de réversibilité après au moins deux cycles de spermatogenèse sans exposition à la chaleur.
... In the other vain, one study shows (Partsch et al., 2000) that scrotal temperature, which closely reflects testicular temperature, is increased in boys wearing disposable plastic lined nappies. The physiological testicular cooling mechanism is blunted and often completely abolished during plastic nappy use. ...
Lifestyle exposures including temperature have been studied in relationship to male reproductive health. In this project, we focused on two main parameters linked to infertility after testicular exposure of temperature. We evaluated the effects of a mild testis temperature increase (+2°C) on sperm morphology and sperm aneuploidy in five healthy men and examined its potential reversibility. We used 27 fertile men for comparison of results (control group), and designed an experimental protocol that induced in five healthy fertile men, an increase of testicular and epididymal temperature by maintained the testes in a supra-scrotal position by means of specially designed underwear worn 15 ± 1 hours daily consecutive days.
The first part of my thesis was dedicated to the study of the effects of a mild testis temperature increase (+2°C) on sperm morphology and multiple anomalies index (MAI). We observed that a significant impact on sperm morphology and MAI as early as days 20 and 34 reflecting an effect on the spermiogenesis and meiosis stages. This drastic effect was present during the entire heated period and recovery of the values before heating was observed at day193.
In the second part, sperm aneuploidies of chromosomes X, Y, 18 were analyzed by fluorescence in situ hybridization (FISH) before, during and after a mild testis temperature increase. We found that a significant increase in total sperm aneuploidy, sex disomy and nullisomy at 45 days post-heating. Moreover, since increased abnormal sex disomy XY18, sex nullisomy and total sperm aneuploidy values were observed at the same time, these effects were completely reversed at least two spermatogenesis cycles after heat exposure.
Our results may have clinical implications in male infertility, the effect of a mild testis temperature increase was reversible but it seems advisable to allow at least one or two cycles of spermatogenesis to pass in order to recover normal exacting function.
Keywords: Temperature, Testis, Sperm morphology, MAI, Aneuploidy, Men,
... Under oxidative stress, the testes elicit a variety of defence tactics such as triggering of antioxidant enzymes, production of heat shock proteins, apoptosis, and cell death. Thermoregulation of testes is interrupted by certain life-style factors and may cause disruption of spermatogenesis such as tight clothing, placing of laptop over the thighs, standing near an active microwave oven, and keeping of a cell phone on hip or in a pants pocket, clinical conditions (cryptorchidsm and varicocoel), and occupational hazards (welders, kiln workers, car, or truck drivers) (Thonneau et al. 1998;Ikeda et al. 1999;Bujan et al. 2000;Partsch et al. 2000;Jung et al. 2005;Mieusset et al. 2007;Sheynkin et al. 2011;Avendano et al. 2012;McGill and Agarwal 2014). Scrotal heat treatments cause oxidative stress and lead to synthesis of reactive oxygen species (ROS -superoxide anion, hydrogen peroxide, and hydroxyl radical). ...
Context:
Hyperthermia causes detrimental effects on the testes leading to fertility problems. Mallotus roxbhurghianus Muell. Arg. (Euphorbiaceae) is used in traditional medicine and possesses antioxidant property. However, the mechanisms remain unknown in the context of alleviative action of M. roxburghianus against heat stress.
Objective:
The objective of this study was to demonstrate the alleviating activity of M. roxburghianus and its mechanism in scrotal hyperthermia.
Materials and methods:
Scrotal hyperthermia experiments were performed in three groups (n = 7 per group) consisting of (i) the control group (C) maintained at 22 °C for 30 min, (ii) the heat stress-induced group (HS), and (iii) the heat stress-induced M. roxburghianus-treated group (HSM - 400 mg/kg each) in a thermostatically controlled water bath at 43 °C for 30 min. Subsequent to the heat treatment HS group, rats were treated with saline p.o and methanol extract of M. roxburghianus was administered to the rats of HSM group along with their standard food for 14 d. Scrotal hyperthermic effects were evaluated.
Results:
Scrotal hyperthermia significantly (p < 0.0001) elevated malondialdehyde levels while decreasing the body and testes weights, serum testosterone, and antioxidant enzyme levels due to oxidative stress. Disorganisation of seminiferous tubules and arrest of spermatogenesis were observed in the HS group. The administration of methanol extract of M. roxburghianus (400 mg/kg) for 14 d after heat treatment significantly suppressed the lipid peroxidation, restored the antioxidant enzyme and testosterone levels, revived the spermatogenesis, and increased the cell proliferation activity in the HSM group.
Discussion and conclusion:
The methanol extract of M. roxburghianus accelerates testicular recovery from the damaging influence of hyperthermia.
... The use of plastic material reduces the skin's breathability, which would lead to a warm and moist perigenital area, thereby contributing to higher scrotal temperature. Partsch et al. [ 70 ] studied 14 neonates (term aged 0-4 weeks) and pre-term with a gestational age of 28-36 weeks (postnatal age 14-85 days), 22 infants (aged 1-12 months), and 12 toddlers (age 13-55 months) and reported that young boys wearing disposable plastic-lined nappies have increased scrotal temperatures compared to those wearing reusable cotton diapers (without protective pants). However, in another study, Grove et al. [ 71 ] found no differences in the scrotal temperature profi les of approximately 70 young boys (aged 3-25 months) wearing disposable diapers with a plastic lining compared to those wearing reusable cotton diapers covered with plastic pants. ...
Testicular temperature is reflected by the temperature of the overlying scrotum. The scrotum is well placed anatomically and is capable of physiologically maintaining a hypothermic testis. However, when normal thermoregulation of the testis is impaired, heat stress can occur, negatively effecting semen quality and sperm concentration, motility, and morphology. A number of factors can disturb thermoregulation and increase testicular temperature including pathological conditions such as varicocele and cryptorchidism, posture, clothing, common lifestyle choices such as use of saunas and warm baths, certain exercises such as cycling, laptop usage and occupations that involve or generate heat, and raised ambient temperature. Often, these factors do not occur alone but in combination with one another, which compounds the negative effect of high testicular heat levels on semen parameters. This chapter discusses physiological thermoregulation in the testis, the impact of its failure on semen quality and enumerates factors that could simultaneously and cumulatively contribute to testicular heat stress. Awareness of the potential risks involved and methods to alleviate prolonged scrotal warming are important in the preservation of male fertility. Simple changes to daily habits could help lessen the impact of increased testicular temperatures on male fertility.
... The deleterious effect of cryptorchidism on later spermatogenesis is believed to be related to increased scrotal temperature during early years. Partsch et al. 18 found that scrotal temperature is increased in boys wearing disposable plastic-lined nappies. ...
Background and aims:
There are anecdotal reports that men who wear (Scottish) kilts have better sperm quality and better fertility. But how much is true? Total sperm count and sperm concentration reflect semen quality and male reproductive potential. It has been proven that changes in the scrotal temperature affect spermatogenesis. We can at least affirm that clothing increases the scrotal temperature to an abnormal level that may have a negative effect on spermatogenesis. Thus, it seems plausible that men should wear skirts and avoid trousers, at least during the period during which they plan to conceive children.
Methods:
and results Analysis of literature concerning scrotal temperature and spermatogenesis and fertility. Wearing a Scottish kilt in a traditional ('regimental') way may have clear health-related benefits. Kilt wearing likely produces an ideal physiological scrotal environment, which in turn helps maintain normal scrotal temperature, which is known to be beneficial for robust spermatogenesis and good sperm quality.
Conclusion:
Based on literature on scrotal temperature, spermatogenesis and fertility, the hypothesis that men who regularly wear a kilt during the years in which they wish to procreate will, as a group, have significantly better rates of sperm quality and higher fertility.
... A marked change in the testicular thermal environment postnatally is an additional factor that might influence the outcome of adult spermatogenesis [44]. Partsch et al. [45] reported the effect of reusable cotton vs. plastic-lined disposable diapers on scrotal temperature during infancy and early childhood. Significant lower recto-scrotal temperature differences, as well as higher mean 24-h scrotal skin temperatures, were observed in all boys wearing plastic-lined nappies. ...
The frequency of defective spermatogenesis and accompanying decreases in sperm parameters such as sperm count and motility
appears to be on the increase. Arguably one of the most compelling reasons for this phenomenon is the influence of environmental
factors on male reproduction. Despite spermatogenesis being a function of only the mature testis, environmental insults during
maternal, perinatal, and prepubertal phases can indirectly influence eventual sperm production in the adult male. It is believed
that exposure during these phases of the developing testis leads to irreversible effects on spermatogenesis, while the accompanying
effects of adulthood exposure are in all probability reversible. This chapter explores the various environmental factors that
can influence spermatogenesis, both directly and indirectly (i.e., exposure during all the stages from the developing fetus
all the way up to and in the adult male). In this overview, not only are the effects of environmental chemicals and toxins
discussed, but the focus is also on several lifestyle factors and occupational exposure that can impinge on the process of
sperm production. Furthermore, the role of epigenetic defects that can result in defects in transgenerational inheritance
due to environmental insults is also investigated briefly. Despite the lack of conclusive studies, it is evident from this
overview that there are enough compelling reasons to believe that the future of male gamete production may be actively affected
by the environment.
KeywordsSpermatogenesis-Environmental-Chemical-Lifestyle factors-Epigenetics-Oxidative stress-Endocrine disrupting-Maternal exposure-Testis
... An example of where the link is somewhat tenuous is in a recent and controversial study of plastic disposable diapers (Partsch et al, 2000). In this study, children wearing these diapers had a mean scrotal temperature that was higher than when they were wearing cotton diapers. ...
When examining the results of a positive research study, one needs to consider two issues of clinical relevance. First, is the outcome measure of direct interest to patients, or is it clearly linked to a measure of direct interest to patients? Second, is the difference large enough to lie outside the range of clinical indifference? Don't accept the findings of a positive research study without a careful consideration of clinical relevance.
... testicular function in adult life. Only well-planned longterm follow-up studies will be able to test this hypothesis (Partsch et al., 2000). ...
Summary The decreasing trends in fertility rates in many industrialized countries are now so dramatic that they deserve much more scientific attention. Although social and behavioural factors undoubtedly play a major role for these trends, it seems premature, and not based on solid information, to conclude that these trends can be ascribed to social and behavioural changes alone. There is evidence to suspect that changing lifestyle and increasing environmental exposures, e.g. to endocrine disrupters, are behind the trends in occurrence of male reproductive health problems, including testis cancer, undescended testis and poor semen quality. These biological factors may also contribute to the extremely low fertility rates. However, the necessary research is complex and requires non-traditional collaboration between demographers, epidemiologists, clinicians, biologists, wild life researchers, geneticists and molecular biologists. This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists.
... In the adult, both germ cells and Sertoli cells appear to be responsive to heat and show changes in the expression of, for example, heat shock proteins [17][18][19]. embryo postnatal/ prepubertal puberty adult pared to air-exposure [41,42]. There appears to be little difference between the use of modern disposable nappies and old-fashioned cloth nappies used together with a plastic cover. ...
The possession of a scrotum to contain the male gonads is a characteristic feature of almost all mammals, and appears to have evolved to allow the testes and epididymis to be exposed to a temperature a few degrees below that of core body temperature. Analysis of cryptorchid patients, and those with varicocele suggest that mild scrotal warming can be detrimental to sperm production, partly by effects on the stem cell population, and partly by effects on later stages of spermatogenesis and sperm maturation. Recent studies on the effects of clothing and lifestyle emphasize that these can also lead to chronically elevated scrotal temperatures. In particular, the wearing of nappies by infants is a cause for concern in this regard. Together all of the evidence indirectly supports the view that lifestyle factors in addition to other genetic and environmental influences could be contributing to the secular trend in declining male reproductive parameters. The challenge will be to provide relevant and targeted experimental results to support or refute the currently circumstantial evidence.
This chapter reviews studies whose results have advanced our knowledge about the effects of fiber-based materials on human skin with the use of bioengineering instrumentation. The emphasis is on how fiber-based materials change properties of the skin they cover and/or contact. Readers are referred to sources of information about the bioengineering instrumentation used. Our purpose is to encourage further work in this area.
The emotional and environmental impact of transitioning from a nappy-free culture to a society dependent on disposable nappies comes at a cost. After a seven-month “baby observation” travelling through Asia, my hypothesis is that the traditional indigenous method of managing the baby’s elimination enhances attunement, bonding, and attachment, and when the child feels held in mind by the mother in this way he is more emotionally regulated and somatically connected. However, the exponential use of disposable nappies may be our blind spot where neither the dangers to the psychological and physical health of the future generation, nor to the planet, are being held in mind. Waitara He utu ka tau ki te taha kare-ā-roto, taha pūtaiao mai i te whakawhitinga i tētahi ahurei kope pātea ki tētahi hapori whakamau kope whiu. I muri mai i te mātakitakinga kōhungahunga i te haerērētanga i Āhia, e whakapae ana au nā te tikanga whakahaere whakaputa para a te kōhungahunga ka hōhonu kē ake te piri te pirihonga, ā, inā rongo te tamaiti i te pēnei o tōna mau ki tōna whāea ka mauri tau ake te atoato. Heoi anō, ko te mahi tautokonga mau kope whiu pea tō tātou whakapuranga kanohi inā te kore e whakaaro ake ki ngā tūpatonga ki te oranga hinengaro oranga tinana ki ngā rēanga o anamata, tae atu hoki ki a Papatuanuku.
This chapter reviews studies whose results have advanced our knowledge about the effects of fiber-based materials on human skin with the use of bioengineering instrumentation. The emphasis is on how fiber-based materials change properties of the skin they cover and/or contact. Readers are referred to sources of information about the bioengineering instrumentation used [28-30]. Our purpose is to encourage further work in this area.
This chapter reviews studies whose results have advanced our knowledge about the effects of Fiber-based materials on human skin with the use of bioengineering instrumentation. The emphasis is on how Fiber-based materials change properties of the skin they cover and/or contact. Readers are referred to sources of information about the bioengineering instrumentation used [28-30]. Our purpose is to encourage further work in this area.
Objective: To study the effect of testicular local heating on spermatogenic cell apoptosis in immature rat. Methods: Forty-eight male SD immature rats were randomly divided into heat treatment group (43 °C, 15 min) and control group (22 °C, 15 min). Each group was further divided into four sub-groups respectively according to the time 2 hours, 6 hours, 24 hours and 14 days after testicular local treatment. The spermatogenic cell apoptosis in all sub-groups was examined by means of electron microscopy and terminal deoxynucleotidyl transferase-mediated dUDP-nick end labeling (TUNEL) method. Results: In the groups of heat treatment except for 2h-group, spermatogenic cell apoptosis was observed by electron microscopy. The percentage of positive TUNEL cells in the 6h heat treatment group was higher than that in the control group (P <0.05), as well, but there was no difference in the percentage of positive TUNEL cells between the 2h heat treatment group and the control group, the percentage of positive TUNEL cells in the 24h and 14d heat treated groups was significantly higher than that in the control groups (P <0.01). Conclusion: Testicular local heating can increase the spermatogenic cell apoptosis in immature rat.
The washable diapers were used until 1960, then they were gradually substituted by disposable diapers (DD). Around 16 millions of children use 24 billions of DD in west Europe. This large quantity of DD raises doubts on environment sustainability. In the last years a reasonable number of parents has chosen the washable nappies; the new models of washable nappies are more comfortable and wearable than old models and they can be washed in washing-machine. This article tries to analyse striking medical features and questions about the use of washable compared to disposable diapers through a literature review. So, paediatricians could help parents to reflect on daily actions in favour of environment substainability from many points of view.
This book examines how ideals of masculinity have long skewed our societal-and scientific-understanding of one of the pillars of male identity: reproductive health. Only with the recent public exposure of men's reproductive troubles has the health of the male body been thrown into question, and along with it, deeper masculine ideals. Whereas once, men's sexual and reproductive abilities were the most taboo of topics, today, erectile dysfunction is a multi-billion dollar business, and magazine articles trumpet male reproductive decline with headlines such as "You're Half the Man Your Father Was." The author looks at our world of plummeting sperm counts, spiking reproductive cancers, sperm banks, and pharmacological cures for impotence, in order to assess the true state of male health. What she finds is male reproductive systems damaged by toxins and war, and proof piling up that through sperm, men pass on harm to the children they father. Yet, despite the evidence that men's health, as much as women's, significantly affects the vitality of their offspring, the author also sees a society holding on to outdated assumptions, one in which men ignore blatant health risks as they struggle to live up to antiquated ideas of manliness.
Seminal quality has deteriorated rapidly over the past 50 years, making it an increasingly prevalent and relevant issue in unexplained male infertility (UMI). Researchers believe that the ever-changing environmental and lifestyle conditions to which the human body is exposed throughout an entire lifespan contribute greatly to this deterioration. Developments in industry and changes in modern lifestyle give rise to a range of different factors such as exposure to chemicals and toxins, harmful environmental agents and adverse lifestyle factors, all of which the body and consequently the reproductive system, has to cope with. Environmental insults during any phase (gestational, childhood and adulthood) of human development can mediate mechanisms disturbing the morphologic, hormonal, or oxidative aspects of testicular tissue and can have severe and irreversible effects on spermatogenesis in a subject or its offspring.
This chapter aims to address some of the most prominent toxins and environmental factors affecting male infertility today, briefly discussing some of the possible effects that these toxins may have as the result of exposure of the male reproductive system to these adverse elements.
Although the analyses of the results of evaluating the effects of environmental factors on the male reproductive system are not without their constraints, this chapter certainly provides enough compelling evidence to conclude that environmental and lifestyle factors play at least some role, if not a definitive one, in the development of UMI.
AIMS To compare two strategies for the eradication of Helicobacter pyloriinfection. METHODS Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment. RESULTS In group 1,H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1 the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%). CONCLUSIONS Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments.
Introduction: The hormonal function of the human testicle is temperature dependant. It requires a temperature 2 – 4 Celow body temperature. The frequency and time of heat exposure are capable of producing reversible or irreversible changes in human spermatogensis. Objective: the aim of this study is to reconfirm or refute the previously tested hypothesis that the occupational heat exposure reduces both sperm output and quality in fertile men due to increases of scrotal and testicular temperature. Materials and methods: Sperm quality was examined in 216 Sudanese workers in sugar factories, Bakeries and Khartoum Foundry center, their ages between 18-54 years old. A scrotal temperature ranged between 38.9-41 Cånd heat exposure for 1 to 24 years were recorded. A 102 age and place-matched unexposed workers who had scrotal temperature range between 32-34 Cas used as a control group. Venous blood (5-10 ml) and semen samples by masturbation were collected from them. Serum was prepared and analyzed for reproductive hormones by RIA techniques. Semen samples were analyzed by Computer Assisted Sperm Analysis (CASA) method. Results: The results of this study indicated that sperms (count, motility and morphology) were assessed in both groups. The sperm density, motility and University Of Gezira
A 4 year old boy underwent cardiac transplantation because of cardiomyopathy with ischaemia. Following transplantation he developed neurological signs of Friedreich's ataxia and the diagnosis was confirmed with genetic testing. Cardiomyopathy is a rare presentation of Friedreich's ataxia and to our knowledge this is the first reported transplant operation for the cardiomyopathy associated with this condition.
Descent of the testis from an intra-abdominal site in foetal life to an extracorporeal location after birth is a mandatory developmental process to ensure that the mature testis promotes normal spermatogenesis. The two phases of transabdominal and inguinoscrotal descent occur approximately during the first and last thirds of gestation respectively. Key anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the cranio-suspensory ligament and a thickening of the gubernaculum. Androgens play a role in both these processes, particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent. Experiments in animals suggest that androgens mediate this effect via the release of calcitonin gene-related peptide by the genitofemoral nerve, but direct evidence for such a mechanism is lacking in humans. The transabdominal phase of descent is under the control of insulin-like 3 (INSL3), a product of the Leydig cells. Definitive evidence of its role in rodent testis descent is illustrated by the phenotype of bilateral cryptorchidism in Insl3-/- null mice. Circulating levels of INSL3 are higher in boys at puberty, are undetectable in girls and are lower in boys with undescended testes. A minority also have a mutation either in the INSL3 gene or affecting its receptor gene, relaxin/insulin-like family peptide receptor 2 (LGRF8). Other factors that may play a role in testis descent include the anti-Mullerian hormone and members of the HOX gene family. Evidence that the prevalence of undescended testis may be increasing provides a phenotypic readout for the effects of postulated chemicals in the environment interfering in some way with the action of factors that control testis descent. Epidemiological studies point to profound geographical variations in prevalence in countries such as Denmark and Finland. Associations have been found with levels of chemicals labelled as endocrine disruptors being higher in breast milk samples from mothers with cryptorchid boys when compared with controls. The adverse effects of these compounds (e.g. bisphenol A) can be replicated in the offspring of dams exposed during pregnancy. A sensitive marker of an anti-androgen effect of a compound is a reduction in the anogenital distance, an anthropometric measurement that is significantly greater in males compared with females. The observation of an association between the anogenital distance in infant boys and the level of pesticides in the urine of their mothers in late gestation indicates that this has the potential to be a useful surrogate marker of the effects of environmental chemicals on testis descent in human population studies. The rightful place for the testis at birth is in the scrotum in order to provide the temperature differential essential for normal spermatogenesis. Appropriate screening programmes and early surgical intervention are the prerequisites to ensure optimal fertility in adulthood and a considerably lessened risk of testis cancer.
We examined trends in the incidence and mortality, and described the survival of patients with penile squamous cell carcinoma in the Netherlands between 1989 and 2006. On the basis of nationwide population-based data, 3-year moving average European age-standardized incidence and 10-year relative survival estimates were calculated. Penile squamous cell carcinomas were categorized according to stage grouping based on the TNM classification. In the 17-year study period, 2000 primary penile cancers were diagnosed in the Netherlands of which 1883 (94%) were squamous cell carcinomas. Median age at diagnosis was 68 years. The majority of patients (57%) were diagnosed with localized tumors (Stage 0 or I). The percentage of missing disease characteristics increased with increasing age. The 3-year moving average incidence rate of patients with penile squamous cell carcinoma increased significantly from 1.4 per 100,000 person-years in 1989 to 1.5 in 2006 with an estimated annual percentage of change of 1.3%. Ten-year relative survival of patients according to the different stage groups was 93% for Stage 0, 89% for Stage I, 81% for Stage II, the 9-year survival was 50% for patients with Stage III disease and a 2-year survival of 21% for patients was found for Stage IV disease. Our study shows that the incidence rate of penile squamous cell carcinoma in the Netherlands has increased slightly, especially the incidence of carcinomas in situ. Patients with Stage III and IV tumors have poor survival.
The onset of spermatogenesis occurs during puberty, before adult blood levels of testosterone are achieved. It can be detected early by the presence of spermaturia.1 Sperm maturation is a temperature dependent process and most male mammals have externally sited gonads to maintain testicular hypothermy. In this issue of ADC , Partsch and colleagues (page 364) report the effect of reusable cotton versus plastic lined disposable nappies (diapers) on scrotal skin temperature during infancy and early childhood.2 Studies in adult men showed a strong correlation between intratesticular and scrotal skin temperatures.3 The use of plastic lined nappies resulted in significantly higher mean 24 hour scrotal skin temperatures in the 48 infants and children studied. The cooling effect of scrotal positioned testes can be quantified by measuring the rectoscrotal temperature difference. In one study of 36 normal adult men, examined in the supine position at room temperature, the mean temperature differential was 2.38°C (range 0.8–5.2°C).4
The intrascrotal cavity temperature in a study of boys treated surgically for cryptorchidism was as much as 4.8°C lower than body temperature.5 The highest rectoscrotal temperature difference in Partsch and colleague's study (2.63°C) was observed in toddlers when clothed in cotton nappies. The temperature differential was blunted in all boys after wearing plastic lined nappies, and abolished altogether in just over a quarter of the boys studied.
How is the testis cooled and what are the functional consequences if this does not happen? Thermoregulatory control mechanisms involve modulation of radiant heat loss through thin scrotal skin, which is devoid of fat, and via a countercurrent heat exchange system in the blood vessels of the spermatic cord.6-8 A higher environmental temperature leads to relaxation of the cremasteric and dartos muscles, increased blood flow to an enlarged scrotal skin surface area, and thus …
To determine the extent of off label and unlicensed drug use in French office based paediatric practice.
A prospective one day survey of all written prescriptions, for patients under 15 years, among 95 office based paediatricians in the Paris, France metropolitan area. Main outcome measures were: comparison of the use of each drug with its product licence for age, indication, dose, and route of administration.
A total of 2522 prescriptions were administered to 989 patients; 844 (33%) were used either in an unlicensed (4%) or an off label (29%) manner. A total of 550 (56%) paediatric patients received one or more off label prescriptions.
Off label prescriptions (that is, outside the terms of the Summary of Product Characteristics) are widespread in office based paediatric practice, while unlicensed drug use is rare in our study. New regulations in the licensing process in Europe are needed to allow children to receive drugs that have been fully evaluated in their specific age group.
Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The effects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances.
A 4 year old boy underwent cardiac transplantation because of cardiomyopathy with ischaemia. Following transplantation he developed neurological signs of Friedreich's ataxia and the diagnosis was confirmed with genetic testing. Cardiomyopathy is a rare presentation of Friedreich's ataxia and to our knowledge this is the first reported transplant operation for the cardiomyopathy associated with this condition.
To compare two strategies for the eradication of Helicobacter pylori infection.
Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment.
In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1 the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%).
Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments.
Editor,—Professor Pharoah questions whether the increased rate of cerebral palsy among newborn infants who were randomly allocated early postnatal dexamethasone therapy in the trial by Shinwell et al 1 might be because dexamethasone increased survival of infants who were impaired before birth, and not because dexamethasone caused cerebral impairment.
However, two recent systematic reviews of randomised trials of postnatal dexamethasone therapy in infants …
Editor,—We were interested to read Dr Robson's leading article regarding alcohol misuse and the reference to acute alcohol admissions to Alder Hey in Liverpool, UK.1 2 We too are concerned by the increasing number of these problems that we see in hospital paediatric practice.
We carried out a retrospective case note review of all the children seen in the Paediatric Emergency department in Sunderland between November …
Editor,—The commentary by Lenney correctly points out that clinicians are often slow to apply good research evidence to clinical practice.1 However, the choice of once daily intravenous gentamicin to illustrate this point is unfortunate. Extended interval aminoglycoside dosing is widely used in paediatric and …
Editor,—We congratulate Olafsdottir et al on their article.1 The sum of the evidence on spinal manipulative therapy (SMT) in the treatment of infantile colic now is that there are 3 randomised controlled trials (RCTs) on the subject.
Two …
Extravagant claims have been made repeatedly in recent years that human sperm counts are falling and that global exposure to environmental estrogens are responsible. The basis for these two distinct claims is reviewed. The claims of falling human sperm output, reviving an old debate, are prompted by a paper by Carlsen et al. (1992). This meta-analysis, however, is marred by numerous flaws that invalidate its claims. Major defects include severe heterogeneity of component studies, rendering them unsuitable for aggregation, and defective data analysis based on arithmetic mean rather than median, which showed no significant changes over time. This debate is likely to remain unresolved until valid, representative population-based studies of human sperm output can be achieved. None have been reported, or seem feasible in the near future, and so alternative strategies, based on surrogate variables for human male fertility not requiring sperm counts, need to be developed and validated. The plausible hypothesis that prenatal estrogen exposure might influence development of the human testis through effects on Sertoli cell replication and sperm carrying capacity has, however, been conclusively refuted by studies of boys born to women exposed to high doses of oral diethylstilbestrol during pregnancy. Neither fertility nor sperm output were adversely influenced by massive maternal estrogen exposure during pregnancy, although minor urogenital malformations did occur. The still wider claims of deteriorating male reproductive health, notably changes in prevalence or incidence of hypospadias or cryptorchidism, also lack convincing population-based evidence, although cancer registry data indicate a gradual increase in testis cancer in some countries. In summary, the available evidence does not support claims of falling sperm counts or any general deterioration in male reproductive health. Population-based studies of valid surrogate variables for male fertility not requiring semen analysis are needed. If population-based evidence regarding male fertility or sperm output could be generated, it is highly unlikely that prenatal estrogen exposure could be a valid explanation of any deterioration as massive maternal exposure to oral estrogen has negligible effects on male fertility or sperm output.
This study investigated the effect of specific, commonly used diaper types on scrotal temperatures in normal healthy, young boys. These included both modern disposable and reusable diapers as well as various types of protective outer coverings that are in common use in both North America and Europe
Scrotal and skin surface temperatures were continuously monitored in healthy, young males using a computerized data-logging system based on temperature probes specifically designed for paediatric studies. These systems could be used either tethered to the PC or made completely portable depending upon the age and activity of the child being measured. Based on our results from several pilot studies, it became clear that the best way to determine if disposable and reusable diapers differ with regard to their impact on scrotal temperatures is to run these comparisons under controlled laboratory conditions where "diaper type" was the primary variable. A 2-h time period was chosen to ensure that sufficient time had elapsed for thermal equilibrium to be established under the diapers. We also felt it necessary to study the impact of urination and simulated this condition over the last 15 min using standardized methods. In addition to the skin surface temperatures, we also measured the temperature of the tympanic membrane using an infrared thermometer as an estimate of "core" temperature for each individual at various times during the session.
In this study, we have clearly shown that scrotal temperatures are the same whether the child is wearing disposable or reusable cloth diapers with a protective cover. The only situation in which scrotal temperatures were found to be lower is when the cloth diaper is used alone without a protective cover but this is not representative of how these products are actually used. We also found that on average scrotal temperatures are significantly lower than core for each diaper type. Occasionally, we did see individuals in which the maximal scrotal temperatures approached core temperatures but in every case the thermal sensors were soiled by a bowel movement. We also found that skin surface temperatures increased not only when covered by a diaper but also due to the thermal insulation provided by outer garments and blankets.
Scrotal hyperthermia has been identified as a risk factor for male infertility. Laptop computers (LC) have become part of a contemporary lifestyle and have gained popularity among the younger population of reproductive age. LC are known to reach high internal operating temperatures. We evaluated the thermal effect of LC on the scrotum.
Right and left scrotal temperature (ScT) was measured in 29 healthy volunteers in two separate 60 min sessions. ScT was recorded from thermocouples on a digital datalogger every 3 min with the working LC in a laptop position and in the same sitting position with approximated thighs without LC.
ScT increased significantly on the right and left side in the group with working LC (2.8 degrees C and 2.6 degrees C, respectively; P<0001) and without LC (2.1 degrees C, P<0.0001). However, ScT elevation with working LC was significantly higher (P<0.0001).
Working LC in a laptop position causes significant ScT elevation as a result of heat exposure and posture-related effects. Long-term exposure to LC-related repetitive transient scrotal hyperthermia is a modern lifestyle feature that may have a negative impact upon spermatogenesis, specifically in teenage boys and young men. Further studies of such thermal effects on male reproductive health are warranted.
The aim of the study was to validate the reliability of samples obtained with urine collection pads (UCP) for selected laboratory biochemical analyses, urine cell microscopy, and bedside semi-quantitative stick urinalysis. A series of laboratory experiments was performed to test agreement between urine concentrations, or results, before and after passage through a UCP (incubated for 37 degrees C for 15 min). The following urinalyses were performed: electrolytes, calcium, phosphate, urate, osmolality, pH, protein, catecholamines, toxicology for drugs of abuse, stick urinalysis for glucose, ketones, protein, blood, leucocytes and nitrites, and microscopy for red and white cells. Close agreement was shown for all laboratory analyses except proteinuria, which was underestimated by, on average, 10% after UCP passage. However, stick urinalysis for proteinuria remains sufficiently reliable for clinical use. UCP substantially retain or destroy red and white cells, but stick urinalysis for blood and leucocyte esterase remains reliable. In conclusion, urine samples derived from UCP show good agreement across a clinically relevant range for the biochemical analyses undertaken in this study. Microscopy of UCP samples is unreliable for cellular material but semi-quantitative stick urinalysis for red and white cells is a satisfactory alternative.
The aim of our study was to interpret the changing incidence, and to describe the mortality of patients with testicular cancer in the south of the Netherlands between 1970 and 2004. On the basis of data from the Eindhoven Cancer Registry and Statistics Netherlands, 5-year moving average standardised incidence and mortality rates were calculated. An age-period-cohort (APC) Poisson regression analysis was performed to disentangle time and birth cohort effects on incidence. The incidence rate remained stable for all ages at about 3 per 100,000 person-years until 1989 but increased annually thereafter by 4% to 6 in 2004. This increase can almost completely be attributed to an increase in localised tumours. The largest increase was found for seminoma testicular cancer (TC) patients aged 35-39 and non-seminoma TC patients aged 20-24 years. Relatively more localised and tumours with lymph node metastases were detected in the later periods. APC analysis showed the best fit with an age-cohort model. An increase in incidence of TC was found for birth cohorts since 1950. The mortality rate dropped from 1.0 per 100,000 person-years in 1970 to 0.3 in 2005, with a steep annual decline of 12% in the period 1979-1986. In conclusion, the increase in incidence of TC was strongly correlated with birth cohorts since 1945. The increase in incidence is possibly caused by in utero or early life exposure to a yet unknown risk factor. There was a steep decline in mortality in the period 1979-1986.
The aim of this study was to interpret changes in mortality from testicular cancer (TC) against the background of changes in treatment and survival in the south of The Netherlands. Five-year moving average standardised mortality rates were calculated. Primary treatment and relative survival were analysed according to histology, stage and year of diagnosis. The mortality rate dropped in the period 1979-1986 and then flattened out. The types of treatment that patients received did not change significantly over time and were according to the guidelines. Ten-year relative survival for seminoma TC patients improved from 81% (67-91%) in 1970-1979 to 95% (88-100%) in 2000-2002; for non-seminoma TC patients these rates were 54% (38-68%) and 92% (85-99%), respectively. Conditional 5-year relative survival for seminoma and non-seminoma TC patients 5 years after diagnosis was 99% and 96%, respectively. In conclusion, there was an enormous increase in relative survival and a significant decrease in mortality.
The concept that an elevation of testicular temperature results in impairment of spermatogenesis is widely accepted. Here, current knowledge concerning genital heat stress and its consequences in men is reviewed. Duration of sitting during work positively correlates with daytime scrotal temperatures and daytime scrotal temperature negatively correlates with semen quality. However, the assumed negative correlation between duration of sitting and semen quality could not be shown in the available studies. Fertility parameters of professional drivers with long periods of sitting in vehicles were impaired; however, for predominantly affected drivers of vans, trucks or industrial heavy machinery potential confounders have to be considered. Wearing tight fitting compared with loose-fitting underwear is associated with significantly higher scrotal temperatures. However, available observations suggesting a link between tight-fitting underwear or trousers and impaired semen quality are not convincing. Studies addressing professional exposure to high temperatures delivered conflicting results concerning fertility parameters. The postulated negative impact of sauna visits on semen quality is not sufficiently underlined by the available studies. Oligozoospermic men with a varicocele have significantly higher scrotal temperatures than normozoospermic men, and according to several studies varicocelectomy normalises scrotal temperatures. A further link has been reported between fever and deteriorated semen quality. Contraception via genital heat stress has been demonstrated using hot sitting baths or insulating suspensors. However, down-regulation of spermatogenesis is inconsistent and unsafe. On the other hand, scrotal and consecutively testicular cooling is able to improve semen quality.
The testicular changes in pneumonia are without clinical manifestations, are non-specific, focal in character, independent of the infecting organisms or the antecedent disease, and vary in severity directly with the total length of the illness. The process is a continuous one, divisible into stages in which the following features are recognizable: (1) cessation of spermatogenesis; (2) degeneration of preformed spermatocytes, spermatids, and spermatozoa; (3) desquamation of altered cells and fragments of the same; (4) formation of giant cells in the tubule walls with subsequent liberation into the lumen; (5) disappearance of all desquamated cells and all those derived from the spermatogonia by mitosis; (6) in some instances thickening of the hyaline layer of the basement membrane. Older lesions are frequently found which continue the structural alteration of the tubules by hyalinosis and destruction of cells until they ultimately disappear. These lesions are not believed to be connected with the present illness. Edema may represent the acute injury in another form, and round cell infiltration suggests that possibly other factors than toxins may have a part in the tissue alterations. In the absence of definite evidence to the contrary, the cause is assumed to be circulating toxins, as Wolbach (12) claims for influenzal cases. The hemolytic streptococcus produced more extensive changes, both epithelial and interstitial, in primary pneumonia occurring during the measles epidemic than when pneumonia followed as a secondary infection; in the latter cases the pulmonary complications covered a relatively shorter period. Measles and epidemic influenza had little apparent effect upon the testes, except that the former caused mild inhibition of spermatogenesis; evidence regarding the latter is inconclusive. The Pfeiffer bacillus was always associated with other organisms, in primary infections and in those following measles. It occurred alone in a few cases after epidemic influenza, but the testicular lesion was not distinctive. The pneumococcus when alone in primary infections or after an epidemic disease produced a uniformly mild picture which was not intensified when associated with the influenza bacillus. Giant cells were much more frequent after influenzal pneumonia regardless of its cause and were associated with large numbers of other desquamated cells. They are formed in the walls of tubules by futile mitotic effort and incomplete protoplasmic separation, the abnormality of the process being further suggested by the early severing of cytoplasmic attachments and rapid desquamation. The series is unique in its uniformity, in the care exercised in the bacteriological examinations, and in the relative freedom from complicating factors.
We carried out a study to estimate the incidence of erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) requiring hospitalization and to determine which drug therapies were associated with these reactions. We reviewed the clinical records of all patients who were hospitalized with these discharge diagnoses at Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash, from 1972 through 1986. During this 14-year period, an average of about 260,000 persons, with demographic characteristics similar to those of the general population, received their care from GHC, and there were about 25,000 admissions to hospitals per year at the GHC hospitals. Based on International Classification of Diseases-Adapted coding, a total of 61 suspect cases of EM, SJS, or TEN were identified from the computerized hospital discharge file. Based on record review and the application of a uniform set of diagnostic criteria, a total of 37 patients (61%) were classified as having EM, SJS, or TEN. Of these, 16 cases (43%) were attributed to drugs administered to these patients prior to hospitalization. The overall incidence of hospitalization for EM, SJS, or TEN due to all causes was 4.2 per 10(6) person-years. The incidence of TEN alone due to all causes was 0.5 per 10(6) person-years. The incidence of EM, SJS, or TEN associated with drug use were 7.0, 1.8, and 9.0 per 10(6) person-years, respectively, for persons younger than 20 years of age, 20 to 64 years of age, and 65 years of age and older. Drug therapies with reaction rates in excess of 1 per 100,000 exposed individuals include phenobarbital (20 per 100,000), nitrofurantoin (7 per 100,000), sulfamethoxazole and trimethoprim, and ampicillin (both 3 per 100,000), and amoxicillin (2 per 100,000). Overall, our data suggest that cases of EM, SJS, and TEN sufficiently severe to require hospitalization are infrequent among outpatients using well-established drug therapies. A continuing challenge is the evaluation of these severe cutaneous reactions that are associated with newly marketed or less frequently prescribed drug therapies.
In France, the use of an official drug adverse reaction assessment method is mandatory since 1984. The method proposes various qualifications for chronologic and semiologic criteria without clear limits. The definitions could vary with the nature of the side-effect. We report here the results of a consensus meeting on drug-induced photosensitivity. Dermatologists and experts in pharmacovigilance studied together how the "French method" could apply to the two variances of drug-induced photosensitivity: phototoxicity and photoallergy.
The current study is designed to examine long-term trends by histologic types of testis cancer in Connecticut. A regression model was used to identify age, period, or cohort as determinants of the time-trend on histologic types of testis cancer. The results from this descriptive epidemiologic study show that the overall age-adjusted incidence rate of testis cancer has increased 3.5-fold in Connecticut during the past nearly 60 years of cancer registration. The rates for seminoma and nonseminoma have been increasing since the mid-1950s and increase in a similar manner for those aged 15 to 49. The largest increase was observed in the age groups 20 to 44 for seminoma and 15 to 34 for non-seminoma. The observed increase was limited to whites. The results from age-period-cohort modeling suggest that the observed increase in seminoma before 1950s could be largely attributable to a period effect, while the increase for cohorts born after about 1910 both for seminoma and for non-seminoma are mainly explained by a strong birth-cohort effect. Therefore, the observed increase in germ-cell testis cancer in this population is likely to continue in the coming years. Thus far, the proposed hypotheses, such as exposure to DES in utero, earlier lifetime exposures to viruses, trauma or unusual amounts of heat to the testis, cannot adequately explain the observed incidence patterns of testis cancer. Analytical epidemiologic studies with large sample size are urgently needed to examine the risk factors responsible for the increase. © 1996 Wiley-Liss, Inc.
Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated postnatally and during and after puberty, may play a crucial role for both the development of the CIS gonocyte and progression of the neoplasm to invasiveness. The reported increase in testicular cancer is not the only sign that male reproductive health is at risk. There are reports that undescended testis and hypospadias have become more common. Also semen quality has deteriorated, at least in some countries. The epidemiological evidence suggests that environmental factors may play a role. Are the environmental hormone disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the apparently synchronised deterioration in these aspects of male reproductive health?
Purpose: Our purpose was to measure changes in semen quality and quantity in young healthy sperm donors in Jerusalem over time.
Methods: A retrospective analysis of semen parameters over 15 years using linear regression analysis, in a single sperm bank in a tertiary university center. Study population consisted of 188 young, healthy medical students, aged 20 to 30 years, who donated sperm samples for Artificial insemination between 1980 and 1995.
Results: There were no statistically significant changes in semen concentration and motility during the study period. The mean semen volume increased by 0.1 ml (5.1%) per year (P < 0.0001), with a concomitant mean rise of 5.8 × 106 (7.7%) per year in total motile sperm count. The percentage normal morphology decreased by a mean of 1.04% per year during the entire period (P < 0.0001).
Conclusions: During the past 15 years, there has been an increase in total motile sperm count, secondary to an increase in semen volume, and a decline in normal morphology that are independent of the age and the duration of abstinence in fertile men.
To establish the clinical, etiological, and prognostic features of acute urticaria in infancy and early childhood and to define its optimal management.
Prospective study. The inception cohort was collected from April 1, 1992, through March 31, 1994. After initial evaluation, the course of the disease was assessed at 2 months and after 1 to 2 years.
Emergency department of a regional teaching pediatric hospital (referral center), which is also the only pediatric hospital for the general community in the city (population, 600,000 inhabitants).
Fifty-seven consecutive infants, aged 1 to 36 months, hospitalized with a final diagnosis of acute urticaria. Follow-up at 1 to 2 years was available in 40 of 57 patients.
Oral antihistamines (dexchlorpheniramine maleate, terfenadine, or hydroxyzine hydrochloride) for 2 weeks.
Recurrence and chronicity.
Annular or geographic papules and plaques with hemorrhagic lesions were seen in 28 patients (49% of cases) and angioedema in 34 patients (60% of cases). An underlying cause was suspected or identified in 52 patients (91% of cases). Infection, either associated or not with drug intake, was the cause in 46 patients (81%) and foods were the cause in 6 (11%). Parasitic infestations were noncontributory. Hemorrhagic lesions and association with articular symptoms were statistically more frequent in urticaria caused by infections. Atopy in the patient or family was associated in 33 patients (58% of cases), and particularly atopic dermatitis was associated with urticaria caused by food. At 1- to 2-year follow-up, 12 (30%) of 40 patients surveyed had chronic or recurrent urticaria.
Causative factors in urticaria are dominated by benign viral illnesses, often associated with antibiotic drug therapy. In most patients, laboratory investigations are not required. Twenty percent to 30% of cases evolve into chronic or recurrent disease.
Testicular development, as measured by testis weight, Leydig cell weight and number of germ cells, was investigated in 5 groups of pigs at 5 weeks after birth. In normal pigs, the left and right testis were developed about equally. In naturally unilateral cryptorchid pigs, the abdominal testis was significantly less developed than the scrotal testis. Expressed as a ratio, the respective values were: testis weight, 0.69; Leydig cell weight, 0.65 and number of spermatogonia, 0.54. Such a reduced development was not found in pigs which were naturally unilateral cryptorchid at birth, but which displayed testicular descent during the second week after birth. In normal pigs which were made unilaterally cryptorchid at 1 day after birth, a comparable reduction of the ratio occurred as in naturally unilateral cryptorchids and the respective values for these were: testis weight, 0.75; Leydig cell weight, 0.70 and number of germ cells, 0.60.
Sham operations did not appear to influence testicular development. From these results it is concluded that 1) it appears unlikely that there is a primary defect in the naturally maldescended testis, 2) birth is a crucial moment for the onset of reduced development in the maldescended testis and 3) a scrotal position from the time of birth is necessary for normal testicular development. It is probable that the higher abdominal temperature is an essential factor causing the reduced development of the maldescended testis from birth onwards.
The Stevens-Johnson syndrome is a multisystem inflammatory disorder associated with a widespread erythematous eruption that can result in death. Although usually considered a pediatric disease, this syndrome frequently affects adults. There are many etiologic associations including drugs and infections; however, the pathophysiology of the syndrome remains obscure. Treatment at present is symptomatic and supportive. Although frequently used, the beneficial role of corticosteroids in this syndrome remains to be proved. The case report describes a young woman who after treatment with several drugs developed the Stevens-Johnson syndrome in association with a Mycoplasma pneumoniae infection. We include a brief review of the literature with emphasis on the Stevens-Johnsons syndrome's association with M pneumoniae infections. Those caring for patients with skin disease should be aware of the association between such treatable infections and this syndrome.
It is generally accepted that the correct treatment for patients with severe erythema multiforme is systemic corticosteroids. This paper is a review of thirty-two paediatric patients with severe erythema multiforme (Stevens-Johnson syndrome) who were treated with either large doses of systemic corticosteroids or supportive care only. Those patients treated with steroids did not recover sooner than those treated in other fashions and the steroid treated group had a significant incidence of medical complications. This retrospective study proves nothing but it does suggest that treatment of patients with the Stevens-Johnson syndrome with systemic corticosteroids may be associated with significant side effects and prolonged recovery.
To investigate whether semen quality has changed during the past 50 years.
Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991).
14,947 men included in a total of 61 papers published between 1938 and 1991.
Mean sperm density and mean seminal volume.
Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density.
There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.
Infantile acute hemorrhagic edema of the skin is not included as a separate entity in the current English-language literature as it is in continental Europe. Therefore we have attempted to clarify the nosologic position of acute hemorrhagic edema among cutaneous vasculitides in children, on the basis of our experience in 10 cases. Our study confirms that acute hemorrhagic edema affects infants between 4 and 24 months of age. The two main features are an ecchymotic purpura, often in a cockade pattern, and an inflammatory edema of the limbs and face. Visceral involvement is uncommon. Spontaneous and complete resolution occurs within 1 to 3 weeks; one to four attacks may occur. Histopathologic examination demonstrates a leukocytoclastic vasculitis. Perivascular IgA deposits can occasionally be found. Besides typical acute hemorrhagic edema, some cases in 2- to 4-year-old children appear to overlap with Schönlein-Henoch purpura. We suggest that typical acute hemorrhagic edema should be regarded as a separate clinical entity. This allows an appropriate prognosis to be made for this generally benign disease of infants.
A case is presented of severe erythema multiforme occurring in a 2-month-old boy from Zimbabwe which was probably triggered by phenobarbitone. He later developed the acquired immunodeficiency syndrome and serological tests suggested that it was a congenital HIV-I infection.
The application of a new, miniaturized portable digital data recorder "Thermoport" (Institute for Reproductive Medicine, Münster, West Germany) for continuous determination of scrotal temperatures revealed great variations of scrotal temperature during 24 hours in normal men. Maximum temperatures approached body core temperatures. Mean scrotal temperatures of 10 normal men rose during sauna from 32.72 +/- 0.23 degrees C to 37.53 +/- 0.38 degrees C. During treadmill running, scrotal temperatures increased by more than 2.5 degrees C. Minimal scrotal temperatures were increased in some men with varicocele compared with normal fertile men indicating impaired cooling mechanisms. The continuous temperature measurements facilitate assessment of temperature dynamics. The miniaturized design of the Thermoport makes it suitable for routine use in outpatients of infertility clinics, in occupational medicine for evaluation of heat hazards, and for investigations of body temperatures under various experimental conditions.
A retrospective study was carried out in 40 infants, age 1 to 24 months, with urticaria. Acute urticaria was seen most frequently (85%), followed by recurrent (10%) and chronic disease (5%). Several clinical features such as frequency of angioedema and hemorrhagic lesions appeared to be specific to urticaria in infants. An underlying cause was identified or suspected in 65% of cases: foods in 25%, and drugs and infections in 37.5%. Under 6 months of age, all infants had acute urticaria and 75% had cow's milk allergy. After 6 months of age, the main causes were drug intake (mostly aspirin and amoxicillin) and/or infections (mainly viral) (50%). Atopy was not overrepresented (20%), although a possible link between atopy and recurrent urticaria was noted. After a follow-up of 2 to 7.5 years, 96% of patients were symptom free. Thus, our results indicate that clinical and etiologic features of urticaria in infants are somewhat different from those of adults and children.
Erythema multiforme is a distinctive hypersensitivity syndrome characterized by skin and mucous membrane lesions and, in its more severe forms, mucosal lesions with constitutional symptoms and, at times, visceral involvement.1,2 It is usually considered acute and self-limiting, but recent observations indicate that it may also behave as a chronic recurrent disorder in many people.1,3,4 The disorder may occur at any age, with its highest incidence in young adults 20 to 40 years of age; as many as 20% of cases are seen in children and adolescents.²
PATHOGENESIS
The pathogenesis of erythema multiforme remains unknown. It appears to represent the end result of a hypersensitivity reaction to a number of infectious and other agents: viral, bacterial, protozoal, fungal, or Mycoplasma pneumoniae (Eaton agent) infection; foods or drugs; immunizations; and a variety of other systemic diseases and physical agents. Whereas drug reactions and malignancies are important causes of erythema multiforme in older persons, infectious diseases are the most common precipitants in children and young adults. The most common cause of erythema multiforme appears to be the virus of herpes simplex; a history of cold sores precedes the development of other lesions by about 3 to 14 days. Recurrences are particularly common in this form of erythema multiforme.4,5
A Negative correlation between spermatozoa output and serum gonadotropin levels, as well as between scrotal temperature and spermatozoa output, has been found in man. However, no studies have been done on the relationship between scrotal temperature and serum gonadotropin levels. This paper reports such data from 212 infertile men. The upper limit for normal scrotal temperature was defined as the 90th percentile value (35.3 C) of a control group of 64 fertile men whose mean serum FSH and LH levels were 6.0 +/- 0.8 (+/- SE) and 6.4 +/- 0.7 IU/L, respectively. This value for scrotal temperature (35.3 C) was used to classify infertile men into 3 groups: bilateral hyperthermia (n = 56), unilateral hyperthermia (n = 40), and bilateral normothermia (n = 116). In the unilateral and bilateral hyperthermic groups serum LH and FSH levels were significantly increased compared with those in the normothermic group. The mean serum testosterone values were similar in all groups. To study the relationships between serum gonadotropin levels or spermatozoa output and scrotal temperature, the infertile men also were divided into classes according to their spermatozoa output. These classes were subdivided into two groups, normothermic or hyperthermic, according to whether the left scrotal temperature was equal to or less than, or more than 35.3 C. For the infertile men whose spermatozoa output was more than 60 X 10(6) spermatozoa/ejaculate (normospermia), there was no significant difference between the serum gonadotropin levels of the normothermic (n = 42) and the hyperthermic (n = 20) groups. Among the oligospermic men (spermatozoa output, 0.1-60 X 10(6) spermatozoa/ejaculate), the hyperthermic group (n = 65) had significantly higher serum gonadotropin levels and significantly smaller testicular volumes than the normothermic group (n = 71). The two oligospermic groups also had significantly higher serum FSH values than the infertile normospermic groups. These results were not linked to the presence of a varicocele or a history of cryptorchidism, as the prevalence of varicocele and cryptorchidism was equally distributed within the groups studied. We conclude that the increase in serum gonadotropin levels in the case of a decrease in spermatozoa output is significantly greater in the presence of associated scrotal hyperthermia.
The association between erythema multiforme (EM) and herpes simplex virus (HSV) infection has long been appreciated, although the exact role which HSV may play in the pathogenesis of this herpes-associated EM (HAEM), is unknown. Previous studies have suggested, but not definitively demonstrated, the presence of HSV in lesions of HAEM. The presence of HSV would support the hypothesis that an immune-mediated response directed against HSV-specific antigens in the skin is central to lesion development in HAEM. The purpose of this study was to examine lesions of EM for the presence of HSV DNA by using the polymerase chain reaction (PCR). In addition, in situ hybridization using an HSV-specific RNA probe was performed to further localize the HSV nucleic acids within the skin. DNA was extracted from formalin-fixed, paraffin-embedded specimens of cutaneous lesions of HAEM and also from EM for which no precipitating factor could be documented, otherwise known as idiopathic EM (IPEM). DNA from lesions of bullous pemphigoid served as a negative control. Using PCR to specifically amplify HSV sequences which might be present, and then performing Southern analysis, we demonstrated HSV DNA in 9/13 HAEM and 6/9 IPEM biopsies. No HSV was detected in six lesions of bullous pemphigoid. In situ hybridization of three cutaneous HAEM lesions using an 35S-labeled HSV-specific RNA probe localized the HSV nucleic acids predominantly to the epidermis. Three biopsies of chronic dermatitis, used as negative controls, did not demonstrate this specific hybridization. These findings confirm the presence of HSV in lesions of HAEM and are consistent with the concept of an HSV-specific immune-mediated pathogenesis for this disease. In addition, most cases of IPEM appear to be herpes associated despite the absence of clinically apparent HSV infection.
A retrospective analysis of 21 consecutive patients hospitalized with either Stevens-Johnson syndrome or toxic epidermal necrolysis was carried out to assess morbidity and mortality rates and to establish the value of a specific management practice. Fourteen children with Stevens-Johnson syndrome and seven with toxic epidermal necrolysis were cared for at the Children's Memorial Hospital, Chicago, between 1978 and 1988. All were managed in a well-staffed medical ward or, when necessary, in the pediatric intensive care unit. Supportive measures included reverse barrier isolation, intravenous fluids and nutritional support, meticulous skin care, early detection and treatment of infection, and daily ophthalmologic examination. No patient was treated with systemic steroids. The mortality rate was zero. Eye complications, consisting of dry eyes or mild chronic symblepharon, were the most significant long-term sequelae.
The treatment of erythema multiforme major with systemic steroids became established during the 1950s. Recently, two retrospective case reviews comparing steroid-treated and nonsteroid-treated groups of patients with erythema multiforme found that these agents may be associated with complications. As a result, many clinicians have become uncertain as to the appropriate therapy of this disease entity. We successfully treated the condition with steroids in two children and one adolescent. The controversy over the potential efficacy of such therapy for erythema multiforme persists, however.
In a prospective clinical study of erythema multiforme (EM), we identified 22 subjects who experienced more than 1 episode. These subjects were young, with an average age of 29 years. They had an average number of 12 previous episodes, with each episode lasting 3 weeks. The average interval between episodes was 4.9 months. We counted the number and location of each skin lesion and found that patients had an average of 188 EM skin lesions at the time of their evaluation. We found the isomorphic phenomenon, that is, lesions appearing at sites of skin trauma, in 19 of the 22 study subjects; photodistribution of skin lesions in 15 of the 22, grouping of the lesions over the elbow and knees in 7 of the 22, and nailfold involvement in 7 of the 22. In this study there was compelling evidence for herpes simplex virus association with recurrent EM. All 22 patients had histories of herpes simplex virus infections preceding at least 1 of their previous episodes of EM. Sera from all study subjects had antibodies to HSV detectable by enzyme immunoassay. None, however, had HSV isolated from the throat at the time of the EM or from an EM skin lesion. All 11 patients who were subsequently tested had positive viral cultures for HSV taken from the suspected recurrent herpes lesion. When 8 EM skin biopsies were examined by indirect immunofluorescence with a monoclonal antibody to the type common HSV glycoprotein gB, all had positive staining of keratinocytes. Only one-third of patients with a single episode of EM had a history of possible herpes lesions preceding EM.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma testosterone, 5 alpha-dihydrotestosterone (DHT), delta 4-androstenedione, dehydroepiandrosterone (DHA) and oestradiol-17 beta concentrations of crab-eating macaques after birth were analysed by RIA. The profiles of plasma testosterone and DHT exhibited four phases: (1) a neonatal phase (0 to 3-4 months of age) with considerable synthetic testicular activity; (2) a phase of 'infancy' (generally up to 29 months of age) during which the values of both androgens were low; (3) a prepubertal phase (generally up to 43 months of age) when circulating values oscillated with wider individual variations, and (4) a pubertal phase when the concentrations increased in parallel and concomittantly with the onset of meiosis and the establishment of spermatogenesis. The testosterone values continued to increase, reaching adult values at about 5-6 years of age, whereas DHT levels tended to stabilize from 4-5 years. Relatively high androstenedione values during the neonatal phase decreased progressively until puberty, then increased again slowly up to the adult stage when they plateaued at about neonatal levels. The DHA levels were high during the first months, decreased at about 1 year, remained stable during infancy and prepuberty and then declined again during puberty. At about 5 years, the values were 28% of those in neonates. There was no evidence of an adrenarche before the first signs of sexual maturity were observed. Oestradiol-17 beta concentrations were high at birth and until 3 months, then decreased and remained steady from 1 year of age until adulthood, except at the onset of puberty (27-30 months of age) when high values were again noted. Our results show that, during the neonatal period, the testis exhibited considerable secretory activity.
Erythema multiforme is said to be rare in childhood and especially in early infancy. Three infants, none older than 1 year, were seen with this condition; all showed typical clinical features. In one of the three infants, no distinctive etiological factor(s) could be found. One was suffering from congenital hepatitis (cause unknown) and another from a staphylococcal infection.
PIP
A large body of research confirms the vulnerable nature of spermatogenesis to relatively small increases in testicular temperature. Other physical properties of electromagnetic and ultrasound waves have additive or synergistic effects to those of heat and allow disruption of spermatogenic processes at minimal temperature elevations. In addition, there is a rebound in sperm count following heat-induced suppression of spermatogenesis. These findings suggest the theoretical viability of testicular heating as a reversible method of male contraception in humans. However, before heating techniques can be used for male fertility control, several questions remain to be investigated. The lowest effective doses and the lowest frequency of application of each method of testicular heating necessary for inducing and maintaining a reliable infertile state must be established. It must be determined whether long-term exposure leads to permanent damage or compromise of testicular elements or functions, and whether exposure to simple heat, electromagnetic waves, or ultrasound induces significant changes in the biological constituents of human semen. Also unclear is the exact mutagenic potential of thermal agents on the human gonads. Another research question is whether scrotal warm sensory input rises during testicular heating to a level that is sufficient to alter body core temperature. Rapidly advancing knowledge of biologic constituents of human semen and the increasingly available detection methods of these constituents will enhance research in these areas. It is through such research that the safety, efficacy, and applicability of thermal manipulation of spermatogenesis as a method of male contraception will be established or refuted.
The authors report 18 children with toxic epidermal necrolysis (T.E.N.). The clinical and laboratory signs, the development of complications and sequelae and the drugs presumed to be responsible are compared with those of T.E.N. in adults. The onset was generally marked by a influenza-like state with development of mucosal signs between the first and the seventh days. The lips and buccal cavity were involved in 16 cases and the eyelids and conjunctiva were involved in 15 cases. Epidermal loss occurred after a variable interval of between one and eight days after the appearance of the erythema. The severity of the epidermal loss, expressed as a percentage of the body surface area, was a poor prognostic factor. Hypoproteinaemia was the most frequently observed laboratory abnormality. The complications were infectious and the 2 deaths in this series were due to septicaemia. Ocular complications were also observed: keratitis, responsible for sequelae such as distichiasis, conjunctival adhesions, sicca syndrome. As in adults, these children were frequently taking multiple drugs. Among the drugs prescribed during the classical interval of imputability, two drugs were particularity noted: phenobarbital and oxyphenbutazone. Treatment should only be undertaken in a specialized unit and is based on the principles of intensive care of burns patients: control of hypovolemia and infection. Ocular sequelae should be prevented by local treatments several times a day.
• Toxic epidermal necrolysis (TEN) is an acute severe exfoliative skin and mucosal membrane disorder with a clinical picture similar to a total-body scald injury. Toxic epidermal necrolysis shares features with severe erythema multiforme seen in Stevens-Johnson syndrome, and is thought by some to be a maximal expression of this syndrome. Drug-related TEN is uncommon in children. Mortalities of 70% have been reported, and death is usually secondary to the bacterial and metabolic consequences of a large open wound. Over the past two years, four children with probable drug-induced TEN were treated successfully. Since the problems of infection, wound care, fluid balance, nutrition, and pain control are similar in TEN and major burn patients, treatment using the principles of burn care may improve survival.
(AJDC 1985;139:499-502)
Intratesticular and scrotal skin temperatures were measured in 34 men undergoing scrotal or inguinal surgical procedures under general anesthesia. Scrotal temperatures were measured before and after a dry scrotal shave. Intratesticular temperature was measured under direct vision with a needle thermistor. Linear regression analysis revealed a strong correlation between intratesticular and scrotal skin temperatures. In addition, simple scrotal shaving significantly decreased scrotal skin temperature. These observations suggest that scrotal skin temperature measurements may be useful to detect elevations of intratesticular temperature and scrotal shaving may be a useful adjunct for testicular cooling.
In order to provide a contraceptive method in man, an attempt at inhibition of spermatogenesis was made by means of thermogenesis induced by artificial cryptorchidism. This experimental protocol consists of pushing up the testicles into the inguinal canal and keeping them there, each day during waking hours, by means of an adapted athletic supporter. Fourteen men volunteered for this protocol during a 6- to 12-month period. They all had a normal semen analysis before starting the experiment. The total sperm count, the sperm count per milliliter, the motility, the motile sperm count per milliliter, and the total motile sperm count dropped significantly after the first or second month; they reached their lowest values after the sixth month and remained stable during the next 6 months. At that time the average values reached were a total sperm count of 12 to 34 X 10(6)/ejaculate, a sperm count of 3 to 10 X 10(6)/ml, a motility of 21% to 34%, a motile sperm count of 1 to 3 X 10(6)/ml, and a total motile sperm count of 4 to 12 X 10(6)/ejaculate.
Indirect methods for measuring testicular temperatures probably give valid results. A change in position from supine to standing resulted in a drop of 0.6° C. in intrascrotal temperature. There was no difference in right versus left intrascrotal temperatures except in standing varicocele subjects, in whom the left intrascrotal temperature was significantly higher (0.3° C.). There was a significantly higher intrascrotal temperature (0.6-0.8° C.) in infertile subjects with varicocele than in a control group. Temperature comparisons between infertile subjects without varicocele and a control group did not yield significant results. A distribution curve of intrascrotal temperatures in infertile subjects without varicocele was bimodal, suggesting the presence of a nonhomogeneous population within this group. There was a relationship between decreased testicular size and deranged morphology and increased intrascrotal temperatures in the subjects studied. Tympanic membrane temperatures appeared to be higher in variococele patients than in a control group.
In order to determine the influence of intrascrotal hyperthermia on testicular function, studies were carried out on human males with the following results:
• 1.1. The mean scrotal-rectal temperature differential (S-R differential) of 36 normal men in the supine position at room temperature was 2.38°C. Changes in posture affected this gradient to some extent. Age apparently had no effect.
• 2.2. The mean S-R differential of 1.75° C. in 21 euspermic individuals, 1.93° C. in 37 oligospermics, and 2.0° C. in 8 men with varicoceles must await interpretation pending the accumulation of sufficient data to warrant statistical evaluation.
• 3.3. Infraclavicular immersion of 8 euspermic subjects in hot baths (38 to 43° C.) resulted in a shift of the median S-R differential from −1.6° C. to +1.2° C., i.e., an inversion of the S-R ratio from 36.1:37.7 to 40.5:39.3, or from 0.96 to 1.03.
• 4.4. In 6 euspermic individuals wearing insulating underwear almost constantly for about 6 weeks, and in a seventh subject who wore the insulating clothing for approximately 14 weeks, the sperm count began to decrease at about the third week after the start of insulation, reaching its lowest point between the fifth to the ninth week. With one exception, the men remained oligospermic for 3 to 8 weeks after omitting insulation and then gradually returned to their characteristic preinsulation sperm output. This was reached, at the latest, by the twelfth postinsulation week in all subjects. No effect on volume of semen was observed. Nor was there any change in the morphology of spermatozoa, with the single exception of the subject who wore the insulation for as long as 14 weeks. A lowering of the mean S-R temperature differential by 1° C. accompanied the suppression of spermatogenesis.
• 5.5. In 20 oligospermic individuals, application of wet heat (43 to 45° C.) to the scrotum for half an hour on 6 alternate days resulted in a decrease in sperm count within 11 to 112 days. In 9 of the men, the drop was followed later by a rebound to levels higher than had prevailed prior to treatment. The wives of 6 of the men conceived within 5 months of start of therapy. All pregnancies were normal.
Modification of spermatogenesis by induced intrascrotal hyperthermia may have practical application not only as a means of controlling fertility, but also as a therapeutic tool in certain cases of oligospermia. These studies are being continued with the aim of elucidating the exact mechanism whereby heat effects such changes in testicular function.
Testicular descent was prevented unilaterally in newborn rats by cutting the gubernaculum testis. Morphological changes due to non-descent of the testes were studied in 16-, 20-, and 24-day-old rats. Scrotal and abdominal temperatures were measured in control rats, and a difference was noted from 16 days and onwards. At 16 days of age the abdominal testes showed an abnormal accumulation of lipid droplets in the Sertoli cells at certain stages of spermatogenesis, and the number of tubules which had developed a lumen was slightly greater than in the scrotal testes. At 20 days of age, some spermatocytes were degenerating in the abdominal testes, especially in the tubular segments where lipid accumulation had been seen earlier. Lipid accumulation was noted in the Sertoli cells in all stages of spermatogenesis and additional ultrastructural signs of Sertoli cell malfunction such as dilatation of the SER and dilatation of the intercellular space between adjacent Sertoli cells was observed. Also the number of tubules containing a lumen was slightly larger in the abdominal testes. At 24 days of age, the number of spermatocytes was reduced in abdominal testes and the morphological changes seen earlier in the Sertoli cells were more pronounced. The function of the blood-testis barrier was investigated by the ability of the tubules to exclude lanthanum, and no differences were found between scrotal and abdominal testes at 16 and 20 days of age. The present study suggests that the earliest morphological changes in experimentally primary abdominal testes may occur in the Sertoli cells.
A case of severe, recurrent erythema multiforme in a 39-year-old man with excellent therapeutic response to thalidomide therapy is reported. The treatment caused the lesions to heal and has prevented recurrence for more than 6 months, up to the time of writing.
The authors analyse 40 cases of erythema multiforme (including twenty children under fifteen) seen over a five-year period at the Sick Children's Hospital in Bordeaux, Bullous erythematous target lesions of the skin were associated, in most cases, with pluri-orificial ulcerations on the mucous membranes and, less frequently, with more or less severe systemic or visceral symptoms. Borderline cases were observed, associating features of erythema multiforme simplex and of Lyell disease with variable degrees of dermoepidermal blistering and epidermal necrosis. Infection (32.5% of cases) is a more common etiology in children than in adults; the main pathogens are herpes simplex virus, vaccinia pox virus, and Mycoplasma pneumoniae. Drug-induced forms (37% of cases), which are more often seen in adults than in children, are usually due to sulfonamides or antiinflammatory agents. In 30% of cases, no etiology could be demonstrated. Attention is drawn to the frequency of facial vespertilial erythema, as well as the possible occurrence of severe conjunctival sequellae. The connections between erythema multiforme, fixed drug-induced eruptions, and Lyell disease are discussed: only the last, which implies dermoepidermal cleavage, can be categorized with erythema multiforme. The staphylococcal scalded skin syndrome, in which the epidermolysin of Staphylococcus aureus type II 71 is responsible for a superficial cleavage, proceeds from entirely different mechanisms and should be regarded as totally distinct from erythema multiforme.
Erythema multiforme (EM), in its modern definition, is an acute, self-limited syndrome with distinctive skin lesions with or without mucosal lesions. Use of the terminology "EM minor" and "EM major" is a reasonable approach to separating the classical mild cutaneous syndrome, as described by Hebra (EM minor), from the usually more severe syndrome, with marked mucosal damage, as described by Stevens and Johnson (EM major). Until objective markers for EM are available, we propose preliminary diagnostic criteria for EM, based primarily on clinical features. Although hundreds of factors have been reported to cause EM, only a limited number are reasonably well documented as possible precipitating agents. Recurrent herpes simplex is an important etiologic factor in EM minor, while mycoplasmal infections and drugs may be associated with EM major. Progress in the understanding of EM will require careful attention to definition and diagnostic criteria and identification of distinct clinical and etiologic subsets within the spectrum of EM.
Semen was collected at weekly intervals for 3 wk before and 10 wk after the sauna exposure at 85 degrees C for 20 minutes. The numbers, morphology, ultrastructure, motility, viability and metabolism of the sperm was assessed. Sperm numbers fell within one wk and slowly returned to normal in 5 wk. The earliest ultrastructural change was swelling of the plasma membrane, followed by an increase in the number of immature forms and disorganization of the arrangement of the mitochondria. Motility, glucose utilization and lactic acid accumulation of the sperm rose temporarily immediately after sauna.
In a prospective study of erythema multiforme, forty-two cases were selected with the use of defined criteria. In thirty-three cases (79%), the erythema multiforme occurred following a lesion of recurrent herpes simplex; in four cases (10%), it was related to administration of a sulfonamide drug. Herpes-associated erythema multiforme (HEM) was largely recurrent erythema multiforme minor and was characterized histopathologically by inflammatory changes, such as spongiosis and exocytosis, and by focal liquefaction degeneration of the basal cell zone of the epidermis. Sulfa-associated erythema multiforme (SEM) was a nonrecurrent illness with widespread cutaneous and mucosal damage associated with prominent histologic necrosis of epidermal cells. The deposition of C3 and fibrin along the dermoepidermal junction and the deposition of IgM, C3, and fibrin around dermal blood vessels by immunofluorescence microscopy were similar in both groups. Although HEM and SEM may have somewhat different clinical and histologic features, there is significant overlap in the pattern of tissue damage.
During a 22-year period 51 cases of Stevens-Johnson syndrome (SJS) occurred in infants and children who ranged in age from 3 months to 14 years. Fifty-six percent of patients had an antecedent upper respiratory tract infection or non-specific viral infection, and 67% had received a prescription medication in the 3 weeks before onset of SJS. Nineteen patients (37%) were treated with adrenocorticosteroid medication during their hospitalization. Age, sex, duration of illness, body temperature on admission and history of antecedent medication were similar for the steroid- and non-steroid-treated patients. Rates of infection and overall complications were significantly greater in steroid-treated patients than in those treated symptomatically. These observations suggest that steroid drugs should not be used for treatment of SJS in infants and children.
Testicular cancer is a disease that predominantly affects young and middle aged men. Our data show that incidence rates have recently increased in men aged 15-54 years in all 13 populations examined, irrespective of whether the populations were at high, moderate or low underlying risk. The annual percentage increase in this age group between 1970 and 1985 varied from 1.9% in the West Midlands, UK, to 6.6% in Miyagi, Japan, with a median of 2.7%. Analysis of the data in two separate age bands, 15-34 and 35-54 years, shows that increases are occurring in both subgroups. This, together with analyses by histological category in Denmark and the West Midlands, UK, indicates that both teratomas and seminomas are increasing in incidence. In contrast to the pattern for incidence rates, testicular cancer mortality rates are now declining in all the nine national populations examined. The time from which mortality rates started to decline varies between populations, and in Poland, a reduction was not observed until the 1980-1985 period. This reflects delay in the uptake of effective chemotherapy for the treatment of teratomas. The decline in mortality, against a background of rapidly increasing incidence in most populations, emphasizes the appreciable improvements in prognosis associated with testicular cancer in recent decades. Although the epidemiology of testicular cancer strongly suggests the presence of environmental risk factors that may be controllable, our ignorance about the nature of these factors precludes any strategy of prevention. Early diagnosis and improved treatment will therefore remain a major focus for the control of this cancer. Our ability to treat testicular cancer is thus a major and necessary achievement given the increase in incidence.
It was recently suggested that erythema multiforme (EM) majus and Stevens-Johnson syndrome (SJS) could be separated as two distinct clinical disorders with similar mucosal erosions but different patterns of cutaneous lesions. To test that hypothesis, we made a single-center retrospective study of severe EM with skin and mucosal involvement. Based on a review of clinical photographs, the skin lesions were reclassified as EM when these lesions were made of typical or raised atypical targets that were located on the extremities and/or the face, or as SJS when these lesions were made of flat atypical targets or purpuric maculae that were widespread or distributed on the trunk. Another investigator who was blinded for that clinical classification related each case to its more probable cause (eg, herpes infection or drug-induced reaction), by using scores derived from the medical charts.
The majority (80%) of 76 cases could be classified as one of the two disorders: 28 as EM (37%), 33 as SJS (43%), and 15 as "undetermined" (20%). By using causal scores, the 76 cases were classified as herpes-induced (n = 18 [24%]), drug-induced (n = 40 [52%]), and "other" (n = 18 [24%]). There was a strong correlation between the clinical classification and the probable cause (K = 0.87, P < .001). Specifically, EM was mostly related to herpes (17 of 28 cases) or to other causes (eight of 28 cases); however, EM was rarely related to drugs (three of 28 cases), while SJS was nearly always related to drugs (28 of 33 cases) and never to herpes.
The results of this study support the suggestion that EM with mucosal lesions and SJS could be distinguished on the basis of two different clinical patterns. In addition, a strong relationship was observed between each pattern and specific causes. This is one more piece of evidence that suggests that EM with mucosal lesions and SJS are actually two different diseases.
Several studies have suggested a population-wide decline in the quality of semen over the past 50 years, but clear evidence for decreasing semen quality in recent decades is lacking.
From 1973 through 1992 we measured the volume of seminal fluid, the sperm concentration, and the percentages of motile and morphologically normal spermatozoa in 1351 healthy fertile men. The data on the semen samples were collected at one sperm bank in Paris. The data in each calendar year were analyzed as a function of the year of donation, the age of each patient, the year of birth, and the duration of sexual abstinence before semen collection.
There was no change in semen volume during the study period. The mean concentration of sperm decreased by 2.1 percent per year, from 89 x 10(6) per milliliter in 1973 to 60 x 10(6) per milliliter in 1992 (P < 0.001). During the same period the percentages of motile and normal spermatozoa decreased by 0.6 percent and 0.5 percent per year, respectively (both P < 0.001). After adjustment in multiple regression analyses for age and the duration of sexual abstinence, each successive calendar year of birth accounted for 2.6 percent of the yearly decline in the sperm concentration and for 0.3 percent and 0.7 percent, respectively, of the yearly declines in the percentages of motile and normal spermatozoa (all P < 0.001).
During the past 20 years, there has been a decline in the concentration and motility of sperm and in the percentage of morphologically normal spermatozoa in fertile men that is independent of the age of the men.
Infertility currently affects at least one man in 20, but we are unable to assess whether it is becoming more prevalent because we have extremely poor past records. Male reproduction has been given little attention scientifically and in medical practice. However, our recent meta-analysis in the BMJ of 61 papers on semen quality, which clearly pointed to a decrease over the past 50 years,1 has been repeatedly quoted in the BMJ,2 3 4 Science,5 and the popular media.
We have already responded to the various technical criticisms, several of which concerned the known limitations of meta-analysis.\*RF6-8\* Though the data for 1970-90 were compatible with a decrease as well as with no change or an increase in semen quality, the cautious general conclusion is that a real decline in semen quality did occur over the full period 1940-90. Three recent reports have found that semen quality has declined among candidates …