Biomedical subjects

C Rolf

Publications and source records attributed to C Rolf.

At least 19 recordsLinked to original sources

PubMed2002

Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation.

OBJECTIVE: Transdermal testosterone gel treatment is an effective androgen substitution therapy with several advantages over conventional substitution therapies. Whereas side-effects due to overdosing of hypogonadal patients are unlikely, testosterone gel application without protection may cause severe side-effects in other subjects (partners, family members) by contamination. Therefore, the risk of testosterone transfer of a newly developed 2.5% testosterone gel preparation was evaluated. DESIGN: In two clinical randomized open single-centre studies on healthy male volunteers the percentage of testosterone remaining on the skin after gel application over time (n = 12) and the possibility of a transfer of testosterone to another person (n = 28) was evaluated. In the second study the endogenous testosterone production in the receiving subjects was suppressed by injecting 400 mg norethisterone enanthate (NETE). RESULTS: After 8 h approximately 60% of testosterone applied to the skin could be recovered. When the skin had been previously washed with water, only about 14% of applied testosterone could be recovered. After intense skin contact with a volunteer who had applied testosterone before on his forearm, no increase in testosterone serum levels could be found in NETE-suppressed men. CONCLUSION: Although considerable amounts of testosterone remain on the intact skin for several hours after evaporation of the alcohol vehicle, contamination of a second, especially female or prepubertal, subject causing side-effects seems very unlikely.

Administration, Cutaneous↗

PubMed2002

Age-related disease pattern in infertile men: increasing incidence of infections in older patients.

In a cross-sectional retrospective study, the age-dependency of semen parameters of men with specific andrological diseases was investigated in 3,698 men (mean age 33 years; range 19-63 years) attending a tertiary referral clinic for couple infertility. In all, 1,853 patients suffered from idiopathic infertility (mean age 33.2 years; range 19-60 years), 388 from infections of the accessory glands (34.2; 20-61), 363 had a history of maldescended testes (32.0; 20-51) and 833 a varicocele (33.6; 20-63). In 172 patients, a varicocele and an infection (34.3; 24-54) and in 94 a varicocele and a history of maldecended testes (32.5; 21-53) were found. Semen analysis was performed according to WHO criteria. An age-related decrease in testicular volume was not observed in any group. Total sperm count decreased significantly with advancing age only in patients with an infection of the accessory glands. We found no evidence for age-dependent progressive deterioration of semen variables in the other groups. It may be concluded that the causes for the spermatogenetic defects in men with idiopathic infertility, a history of maldescended testes or varicocele are acquired before adolescence and do not progress during adulthood. In contrast, infections of the accessory glands may lead to decreased sperm counts by functional impairment or partial occlusion of the seminal ducts. Thus, if in the general population declining sperm counts are observed, genital tract infections may be suspected as a contributing factor.

Adult↗

PubMed2002

Germ cell transplantation into X-irradiated monkey testes.

BACKGROUND: An intense debate is ongoing regarding options for fertility protection in oncological patients. Germ cell transplantation has been applied to restore mouse spermatogenesis. Here, an attempt to apply autologous germ cell transplantation to a primate animal model is described. METHODS: Five adult male cynomolgus monkeys were biopsied to retrieve and cryopreserve germ cells before both testes were irradiated (dose 2 Gy). Six weeks later, each monkey received an infusion of its own cell suspension into the right testis, while the left testes were infused with saline. Testis size, sperm counts and serum concentrations of inhibin, FSH and testosterone were analysed weekly for 9 months. Spermatogenic recovery was determined histologically at the end of the study. RESULTS: In four monkeys, the germ cell-infused right testes showed a slight to moderate increase in the rate of regrowth in comparison with the left testes. In two monkeys the right testis proceeded to recover more prominently, resulting in larger right testis volumes and better or full spermatogenic recovery at the study end. Restoration of spermatogenesis occurred as an all-or-nothing event. Inhibin B concentrations increased, while FSH and testosterone concentrations decreased with testicular regrowth. Sperm counts did not recover. CONCLUSIONS: The present study demonstrates the immaturity and complexity of germ cell transplantation as a clinical approach.

Animals↗

PubMed2002

Sperm aneuploidy rates in younger and older men.

BACKGROUND: In order to assess the possible risk of chromosomal abnormalities in offspring from older fathers, we investigated the effects of age on the frequency of chromosomal aneuploidy rates of human sperm. METHODS AND RESULTS: Semen samples were collected from 15 men aged <30 years (24.8 +/- 2.4 years) and from eight men aged >60 years (65.3 +/- 3.9 years) from the general population. No significant differences in ejaculate volume, sperm concentration and sperm morphology were found, whereas sperm motility was significantly lower in older men (P = 0.002). For the hormone values, only FSH was significantly elevated in the older men (P = 0.004). Multicolour fluorescence in-situ hybridization was used to determine the aneuploidy frequencies of two autosomes (9 and 18); and of both sex chromosomes using directly labelled satellite DNA probes on decondensed sperm nuclei. A minimum of 8000 sperm per donor and >330 000 sperm in total were evaluated. The disomy rates per analysed chromosomes were 0.1-2.3% in younger men and 0.1-1.8% in older men. The aneuploidy rate determined for both sex chromosomes and for the autosomes 9 and 18 were not significantly different between the age groups. CONCLUSIONS: The results suggest that men of advanced age still wanting to become fathers do not have a significantly higher risk of procreating offspring with chromosomal abnormalities compared with younger men.

Adult↗

PubMed2002

Natural transmission of a partial AZFb deletion of the Y chromosome over three generations: case report.

The natural transmission of microdeletions of the Y chromosome is occasionally reported in the literature. Here we describe the natural transmission of a partial AZFb deletion over three generations. PCR amplification of several sequence tagged site markers in the three AZF regions of the Y chromosome was carried out in a patient with oligoasthenoteratozoospermia, his father and his naturally conceived son. The deletion was confirmed by Southern blotting. The propositum, his father and his son showed a probably identical, partial deletion of the distal part of the AZFb region, involving sY130 and sY143. The deletion was confirmed by Southern blotting using the sY130 probe. Partial AZFb microdeletions can be associated with moderate oligozoospermia allowing natural conception and therefore natural transmission of this genetic anomaly. Further studies are needed to define the pathogenetic significance of microdeletions involving sY130 and sY143.

Adult↗

PubMed2002

Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study.

INTRODUCTION: In healthy men, body weight and total fat content increase with advancing age, while serum testosterone levels decrease. In order to elucidate whether a causal relationship between these phenomena exists, we investigated the influence of testosterone or human chorionic gonadotrophin substitution on body mass index (BMI), total fat mass and serum leptin in testosterone-treated and untreated hypogonadal patients in comparison with ageing eugonadal men. METHODS: In a cross-sectional study, the inter-relationships of body weight, total fat mass, serum sex hormones and leptin were analysed in untreated hypogonadal men (n=24; age 19-65 years), treated hypogonadal men (n=61; age 20-67 years) and healthy eugonadal men (n=60; age 24-78 years). Total fat mass was assessed by bioimpedance measurement. Univariate and multiple linear regression analysis was used to detect possible differences. RESULTS: In eugonadal men, serum testosterone levels decreased with advancing age (correlation coefficients: r=-0.71; P<0.0001), while BMI (r=0.39; P=0.002), total fat content (r=0.51; P<0.0001) and leptin (r=0.48; P<0.0001) increased significantly. In untreated hypogonadal patients, an increase in BMI (r=0.50; P=0.013) and total fat mass (r=0.41; P=0.044) was also observed with advancing age. However, in substituted hypogonadal patients, no age-dependent change in BMI (r=0.067; P=0.606), body fat content (r=-0.083; P=0.522), serum testosterone (r=-0,071; P=0.59) or serum leptin (r=-0.23; P=0.176) was found. CONCLUSION: Since testosterone-substituted older hypogonadal men show BMI and fat mass similar to those of younger eugonadal men and since non-treated hypogonadal men are similar to normal ageing men, testosterone appears to be an important factor contributing to these changes. Thus ageing men should benefit from testosterone substitution as far as body composition is concerned.

Adipose Tissue↗

PubMed2002

Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men.

OBJECTIVE: In a phase I single-centre, open, randomized study, the pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5% testosterone were evaluated in 26 healthy male volunteers. DESIGN: To eliminate the influence of endogenous serum testosterone, gonadotrophins and endogenous testosterone secretion were suppressed by a single intramuscular injection of 400 mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g testosterone gel daily for 10 days. Half the men in each group washed the gel off 10 min after it had been applied. RESULTS: In all the men, a marked suppression of LH, FSH, testosterone, dihydrotestosterone (DHT) and oestradiol was observed after norethisterone treatment. Physiological serum concentrations of testosterone were restored during the 10-day treatment period in the group of men applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not exceed normal values. Washing 10 min after gel application did not influence the resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to achieve physiological serum concentrations of testosterone. CONCLUSION: Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not influence the pharmacokinetic profile and thus significantly reduces the risk of contamination of female partners or infants.

Adult↗

PubMed2001

Screening for eligibility in the study of antihypertensive medication in children: experience from the Ziac Pediatric Hypertension Study.

BACKGROUND: The FDA Modernization Act has resulted in an increase in pediatric trials of antihypertensive medications. As experience is limited in children to guide the planning of these studies, we reviewed data from the Ziac Pediatric Hypertension Study to determine patterns of early study termination to help future studies. METHODS: For inclusion, subjects aged 6 to 17 years were required to have an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile at the last of three visits during 2 weeks of single-blind placebo screening. Early study termination was defined as early termination for any reason. Screening termination was defined as normalization of blood pressure (BP) during the placebo screening phase. RESULTS: Early study termination rate was 27% (38 of 140 subjects). The most common reason was screening termination due to normalization of BP, accounting for 63% of all early study terminations. Among screening termination subjects who completed three screening visits, SBP was higher (P < .001) at visit 1 (129+/-8 mm Hg) than at visit 2 (123+/-7 mm Hg) or visit 3 (121+/-8 mm Hg), but did not differ between visits 2 and 3. Screening termination occurred in 15% with isolated SBP hypertension, and 21% with isolated DBP hypertension. At randomization, 83% had SBP hypertension and 53% had DBP hypertension. CONCLUSIONS: These data suggest that SBP hypertension should be part of inclusion criteria to increase enrollment and reduce the rate of screening termination, and that 1-week placebo screening is necessary and sufficient to minimize inclusion of transiently hypertensive subjects.

Adolescent↗

PubMed2001

Stress fractures of the tibia: can personality traits help us detect the injury-prone athlete?

One of the few serious drawbacks associated with running is overuse injuries such as stress fractures of the tibia, which cause local pain and swelling, often resulting in a temporary cessation of training. Whereas some runners rarely become injured, others experience recurrent injuries even during fairly short periods of time. The aim of the present study was to compare selected personality traits in a group of runners who had sustained a previous tibial stress fracture (n=17), with a matched group of runners (n=17) who had never experienced stress fractures. The results indicated that the injured runners, especially the women, scored higher than the non-injured runners did on inventories measuring both the Type A behavior pattern and exercise dependency. Since motivation, ambitiousness, and competitiveness are integral parts of these inventories, high scoring individuals might be part of a high-risk population for running injuries, the more so if the individual also feels dependent on regular running for managing stress related mood states, which was the case particularly for the injured women in the present study. However, the somewhat limited number of runners who had had a confirmatory scintigram, which was a criterion for inclusion in the study, warrants a cautious interpretation of the results. The findings nevertheless suggest that in order to prevent recurrent injuries, health education professionals and clinicians ought to focus on conveying the importance of detecting precursors of injury, and the subsequent steps which should be taken to avoid developing a serious injury.

Adult↗

PubMed2001

Immune function in Swedish élite orienteers.

During 1979-1992 an increased frequency of sudden unexpected cardiac death (SUD) occurred among young male Swedish élite orienteers. Subacute-to-chronic myocarditis was found in 12/16 (75%) at autopsy and Chlamydia pneumoniae, or a cross-reacting agent, was suspected on the basis of diagnostic tests performed. Because myocarditis is an infrequent cause of SUD and clusters of SUD are rare, whereas Chlamydia pneumoniae infections are ubiquitous and seldom cause severe myocarditis, 119 top ranked élite orienteers (67 males and 52 females) and 36 highly trained male middle-distance runners and cross-country skiers, serving as controls, underwent immunologic screening in an effort to reveal possible immune dysfunction. Except for two orienteers and one runner/skier who showed genetic C3-deficiency or IgA-deficiency, the results showed no significant differences between the orienteers and controls with respect to immunoglobulin levels, complement activation, lymphocyte subsets, including activated T lymphocytes, and sIL-2r-alpha. IL-1 beta, IL-6, TNF-alpha, and sCD8, tested in the orienteers only, were normal. However, IFN-gamma was significantly higher in controls than in orienteers, who showed normal levels, whereas the orienteers had increased sELAM-1 and sICAM-1 levels. Finally, sIL-2 receptor-alpha was similarly elevated in orienteers and controls. We conclude that, with the tests employed, no immunologic disturbance could be revealed in the orienteers that may potentially have increased their susceptibility to myocarditis and SUD.

Adolescent↗

PubMed2001

Occupational risks for male fertility: an analysis of patients attending a tertiary referral centre.

The impact of environment and occupation on male fertility is still under debate. We investigated whether certain occupations may be over- or under-represented among men attending our infertility clinic in relation to the entire population of the area. Diagnoses and semen parameters of 2054 infertile men from the district of Münster were analysed retrospectively. The patients were categorized into 29 occupational groups. The relative size of each group was compared with that of the entire population in the district of Münster. Farmers were over-represented compared with the general population. Farmers and painters/varnishers showed a significantly higher proportion of reduced sperm counts [odds ratios (OR): 2.13 and 2.17, 95% confidence intervals: 1.18-3.88 and 1.02-4.65] and severely reduced sperm concentrations compared with the entire group of infertile men; in addition, significantly more farmers presented with a history of maldescended testes than other occupational groups (OR: 2.76 and 2.84; CI: 1.12-6.75 and 1.27-6.34). Metal workers/welders formed significantly higher proportions of patients with reduced sperm motility (OR: 5.99; CI: 1.38-26.00). The relatively poor semen parameters of the painters/varnishers could be caused by exposure to toxins. This may also apply to the farmers (fertilizers, herbicides); however, the elevated rate of maldescended testes suggests an effect of exposure during prenatal development or a genetic cause. The findings for metal workers/welders may be because of heat or toxins at the workplace. The study demonstrates that certain occupations are preferentially associated with male infertility.

Adult↗

PubMed2001

Reproductive functions, fertility and genetic risks of ageing men.

The changes of reproductive functions, fertility and genetic risks of ageing females have been investigated relatively intensively. The state of knowledge about endocrine and reproductive changes in ageing men as well as possible age-related paternal genetic risks lags far behind. In general serum testosterone levels decrease with increasing age. In ageing men testis morphology and semen production can be absolutely normal. However, in some testes degenerative forms of germ cells can be observed. Fertility may be maintained up to a very high age. The genetic quality of sperm produced by older men may be reduced for several reasons, among which age-related increases in germ cell mutations, impairment of DNA-repair mechanisms and apoptotic processes are the most likely. The incidence of several autosomal dominant diseases, such as achondroplasia, polyposis coli, Marfan syndrome, Apert syndrome or basal cell naevi is associated with advanced paternal age, whereas there is no clear evidence for a paternal effect on structural or numeric chromosome anomalies. Hence even if offspring of older men have a slightly increased incidence of certain genetic diseases, the individual risk of such a new disease must be considered as extremely small, as the incidence of these diseases is very low.

Aging↗

PubMed2001

Antibodies to Chlamydia pneumoniae in young Swedish orienteers.

During 1992-93 sera from 1790 Swedish elite orienteers were tested for antibodies to Chlamydia pneumoniae. The reason for this was that a cluster of 16 cases of sudden unexpected cardiac death had occurred among Swedish orienteers and DNA from C. pneumoniae had been found in the myocarditic heart and in the lung in 1 of 2 deceased athletes in whom testing was feasible; in addition, C. pneumoniae IgG was found in all 5 cases where serum was available. Among the orienteers, the prevalence rates of IgG antibodies in males and females were 54% (n = 1194) and 50% (n = 596), respectively. The corresponding figures for 319 male and female blood donors were 60% (n = 169) and 53% (n = 150), respectively. These differences are not statistically significant. Male orienteers had a lower prevalence of IgA antibodies than male blood donors (19% and 26%, respectively; p < 0.05), while no such difference was found in females (16% and 18%). The prevalence of IgM antibodies was < 1% in all groups. Neither the performance level of the orienteers nor the place of residence affected the antibody prevalence. In conclusion, Swedish orienteers do not show a higher prevalence of antibodies to C. pneumoniae than healthy blood donors.

Adolescent↗

PubMed2001

Serological and epidemiological analysis of the prevalence of Bartonella spp. antibodies in Swedish elite orienteers 1992-93.

The emergence of the popular, physically demanding and highly nature-interactive sport of orienteering was marked in Sweden by an elevated rate of sudden unexpected cardiac deaths in young competitors during the years 1979-92, with a common underlying cause or causes suspected. Subsequently, sera were collected during 1992-93 from the elite segment of orienteers holding a nationally ranked position, and a survey compiling various epidemiological data was performed. In this study, a total of 1136 sera were analyzed by indirect-fluorescent antibody assay for the presence of IgG antibodies against 3 Bartonella spp.: B. henselae, B. elizabethae and B. quintana. In total, 31% (355/1136) were seropositive for at least 1 species of Bartonella, with titers ranging up to 1/512; 350/1136 (31%) had antibodies against B. elizabethae, 34/1136 (3.0%) against B. henselae and 16/1136 (1.4%) against B. quintana. Males and females showed equal rates of 31% seropositisity to Bartonella spp. (males 241/766; females 114/370). In comparison, 322 time-matched sera from healthy blood donors had antibodies to Bartonella spp. in 6.8% of cases (p < 0.001). The observed high prevalence of Bartonella spp. antibodies found in Swedish elite orienteers may be indicative of a connection with risk factors for the development of myocarditis and sudden unexpected cardiac death.

Adolescent↗

PubMed2001

Subacute bartonella infection in Swedish orienteers succumbing to sudden unexpected cardiac death or having malignant arrhythmias.

During the period 1979-92, an increasing number of sudden unexpected cardiac deaths (SUCD) occurred in young, Swedish, male elite orienteers. Myocarditis was the most common diagnosis in the 16 victims, and in 4 cases was also associated with fatty infiltration mimicking arrhythmogenic right ventricular cardiomyopathy (ARVC). Tissues from autopsies of 5 orienteers were tested for Bartonella by PCR targeting the gltA (citrate-synthase) gene. The products were then sequenced. Antibodies to B. henselae, B. quintana and B. elizabethae were measured by indirect fluorescence antibody assay. Bartonella spp. DNA was detected in the hearts of 4 deceased orienteers, and in the lung of a fifth deceased case. The sequences were close to B. quintana in 2 cases and identical to B. henselae in 3. Four of these 5 cases, as well as 2 additional cases of elite orienteers with ARVC, indicated antibodies to Bartonella. It is suggested that Bartonella-induced silent subacute myocarditis, eventually leading to electric instability, caused the increased SUCD rate among the Swedish orienteers. It is further suggested that Bartonella infection may be a major pathogenetic factor in the development of ARVC-like disease. Although the mode of transmission is unknown, both zoonotic/vector-borne and parenteral person-to-person transmission may be involved.

Adult↗

PubMed2001

Thallium-201 myocardial imaging at rest in male orienteers and other endurance athletes.

During the period 1979 to 1992, 16 sudden unexpected cardiac deaths were known to have occurred in young Swedish orienteers. Autopsy indicated myocarditis to be the most frequent finding, most often combined with extensive myocardial fibrosis. The aim of the present investigation was to explore whether young male orienteers show a higher frequency than other young elite endurance athletes (controls) in the occurrence of Thallium-201 myocardial perfusion defects at rest, suggestive of fibrosis evoked by myocarditis. Thallium-201 perfusion abnormalities at rest were more frequently found in the controls than in the orienteers (26% vs. 12%, p=0.03). Uneven Tl-201 perfusion was associated with left ventricular mass (r=0.32, r=0.24, p<0.01, p=0.02) and body weight (r=0.30, r=0.31, p<0.01, p=0.03) in orienteers and controls, respectively. Echocardiographic left ventricular wall motion abnormalities were found in 11 athletes (9 orienteers and 2 controls) but only two displayed an abnormal Thallium-201 perfusion scan at rest. Perfusion abnormalities at rest did not occur more frequently in the orienteers but were commonly found in both groups of apparently healthy athletes making it futile to discern abnormals from normals. Thallium-201 perfusion aberrations were not associated with left ventricular wall motion abnormalities obtained by echocardiography.

Adult↗

PubMed2000

Alteration of patellofemoral contact during healing of canine patellar tendon after removal of its central third.

Alterations of the patellofemoral (PF) contact pressure and area were assessed using pressure-sensitive film after the removal of the central third of patellar tendon (PT) with healing over time in twelve dogs. The contralateral knee served as control. Histological sections were prepared for descriptive evaluation. No alterations in PT strain, PF contact pressure and area were measured immediately after the removal of the central third of PT compared with that before its removal. Compared with contralateral control, the healing of the donor PF induced a significantly increased PF contact area but not PF contact pressure in the specimens harvested at 6, 12, and 18 months after operation. Increased PF contact area indicated a proximal shift of the PF joint contact during flexion, which was associated with an increased strain of the healing PT under loading. The healing PT became hypertrophic compared with control, but the differences in the cross-sectional area were reduced over time. Histologically, a poorly organized extracellular matrix was observed at 6 months, with a progressive improvement in collagen fiber alignment up to 18 months postoperatively. The results of this study suggest that the removal of the central third of PT does not immediately change PF contact pressure and areas. However, remodeling of the healing tendon may cause an elongated PT, resulting in an increase in PF contact area under a given quadriceps force by knee extension.

Animals↗

PubMed2000

Removal of the lateral or medial third of patellar tendon alters the patellofemoral contact pressure and area: an in vitro experimental study in dogs.

OBJECTIVES: To compare patellofemoral contact pressure and areas after immediate removal of the lateral, central, or medial third of patellar tendon. DESIGN: In vitro experiment in 12 dogs. BACKGROUND: Alteration of the vector sum of the quadriceps muscle contraction after removal of partial patellar tendon might result in changes of patellar tracking in the trochlea. METHODS: Patellofemoral contact pressure and areas were recorded using Fuji pressure-sensitive film at 45 degrees, 60 degrees, and 90 degrees of knee flexion under an isometric quadriceps force of 100% body weight. The patellofemoral contact imprint from the intact knees were obtained as control, and the lateral (n=4), central (n=4), and medial (n=4) third of the patellar tendon were subsequently removed and the patellofemoral contact imprint was recorded. RESULTS: The patellofemoral contact area was found to increase with increasing knee flexion angles. No change in patellofemoral contact pressure and areas was found after removal of the central third patellar tendon. However, after removal of either lateral or medial third of patellar tendon, the patellofemoral contact was rotated with increasing knee flexion angles. This was due to the altered vector sum of the quadriceps force, resulting in significantly decreased patellofemoral contact areas and simultaneously a significantly increased contact pressure, characterized with concentration of patellofemoral contact pressure on both lateral and medial facets of the patellofemoral joint. CONCLUSIONS: The results suggest that removal of the central third of patellar tendon may not alter the patellofemoral contact pressure and areas as compared with removal of either lateral or medial third of patellar tendon that may result in an altered postoperative tracking mechanism of the patellofemoral joint immediately after operation. RELEVANCE: Findings of this in vitro animal study supports the use of central third of patellar tendon as autograft for anterior cruciate ligament reconstruction. However, further experimental studies are needed to investigate how the postoperative healing of the host patellar tendon will influence the findings obtained from this in vitro study.

Animals↗