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At least 19 recordsLinked to original sources

Preputial variability and preferential association of long phimotic foreskins with penile cancer: an anatomic comparative study of types of foreskin in a general population and cancer patients.

Difficulty in foreskin retraction and phimosis are risk factors for penile carcinoma that may be related to the anatomically variable length of the foreskin. This observation has stimulated us to postulate the hypothesis that foreskin length is related to penile cancer. To compare the foreskin in the general population and patients with penile cancer, an anatomic classification of foreskin was designed. We examined the foreskin of 215 uncircumcised males without cancer (age range 15-93 years) and the foreskin of 23 patients with cancer (age range 31-90 years). Foreskin types were classified as long (with the preputial orifice located beyond glans meatus and entirely covering the glans), medium (with the preputial orifice located between meatus and glans corona), and short (with the preputial orifice located between corona and coronal sulcus). Phimosis was defined as a nonretractable prepuce of the long type. We found that 77% of noncancer population cases had long foreskin and that only 7% of these cases were phimotic. Cancer patients showed long foreskin in 78% of the cases, and phimosis was significantly frequent in this group (52%) as compared with the other (p <0.001). Coexistence of a long foreskin and phimosis may explain the high incidence of penile cancer in some geographic regions. To better document these findings, a comparison of foreskin types in countries with high and low incidence of penile cancer will be interesting. However, because phimosis appears to be a major factor, the presence of long foreskin may be a necessary but not a sufficient condition for cancer development. For these reasons we support preventive circumcision in patients with long and phimotic foreskins living in high-risk areas. Cancers not related to long foreskins and phimosis may be causally different.

Adult↗

Differential regulation of bradykinin receptor density, intracellular Ca2+, and prostanoid release in skin and foreskin fibroblasts. Effects of cell density and interleukin-1alpha.

1. Bradykinin (BK) receptors, cytosolic Ca2+, and prostanoids were studied in human skin and foreskin fibroblasts. 2. Bmax values of BK receptors were higher in foreskin than in skin fibroblasts, increasing with cell densities in both cell types. IL-1alpha-dependent receptor induction was blocked by cycloheximide. 3. BK-stimulated cytosolic Ca2+ elevation was higher in confluent than in non-confluent cultures and larger in foreskin than in skin fibroblasts. Responses were not enhanced after IL-1-alpha-induced up-regulation of BK receptors. 4. Intrinsic prostanoid production was higher in foreskin than in skin fibroblasts at comparable cell densities. In foreskin, but not in skin fibroblasts, BK stimulation increased the release of PGE2 10 fold and that of 6-oxo-PGF1alpha 6-7 fold. 5. Preincubation with IL-1alpha had a marked effect on prostanoid release in foreskin fibroblasts only. Subsequent BK stimulation increased the release of PGE2 and 6-oxo-PGF1alpha 7-10 fold in skin fibroblasts while this increase was only 30% in foreskin fibroblasts. Release of TXA2 reached values up to one third of the other prostanoids. The IL-1alpha induced rise in BK-stimulated PGE2 synthesis was fully abolished by specific inhibition of cyclo-oxygenase 2. 6. IL-1alpha sensitized BK-stimulated prostanoid synthesis and modulated prostanoid patterns differently in fibroblasts from skin and foreskin. The IL-1alpha effects on prostanoid release were not related to BK receptor numbers nor to the BK-stimulated Ca2+ signal but appear to be due to induction of prostanoid synthesizing enzymes. Foreskin fibroblasts seem to be unique and significantly different from fibroblasts of other skin locations in respect to their response to inflammation-associated kinins and cytokines.

6-Ketoprostaglandin F1 alpha↗

Foreskin preservation in penile surgery.

PURPOSE: Most hypospadias repairs performed in the United States involve the removal of any foreskin that is not used in the repair, resulting in a circumcised penis. Occasionally, the wishes of the parents or the child are for the final appearance to be that of a normal uncircumcised penis. We report our collective experience from 4 institutions in the reconstruction of the foreskin during penile surgery. MATERIALS AND METHODS: A total of 58 patients underwent penile surgery with reconstruction of the foreskin during a 6-year period. Of the patients 49 underwent hypospadias repair, 8 underwent phalloplasty for chordee correction without hypospadias and 1 underwent reconstruction of the foreskin for a dorsal hood without hypospadias or chordee. Of the 49 hypospadias repairs 46 were distal, 2 mid shaft and 1 proximal shaft. The technique for foreskin reconstruction consisted of a multilayered reapproximation of the lateral margins of the dorsal hood after completion of the urethroplasty and glanuloplasty. RESULTS: Among 49 hypospadias repairs 2 patients had dehiscence of the reconstructed foreskin, with development of a urethral fistula in 1. Of the 58 total patients undergoing penile surgery 56 had retractable foreskin, of whom 4 required postoperative steroid application. Three patients/parents requested a secondary circumcision, 2 for an unacceptable cosmetic result and 1 based on personal preference. CONCLUSIONS: Foreskin reconstruction in association with penile surgery can be performed safely and with a low complication rate in appropriately selected patients. Cases with a higher risk of complications include those involving more proximal hypospadias and those requiring complete degloving of the penile shaft. Of the reconstructions resulting in phimosis most can be salvaged with the application of steroids.

Child↗

Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture.

Numerous studies have indicated a protective effect of male circumcision against acquisition of human immunodeficiency virus (HIV)-1. We investigated mechanisms responsible for the possible increased HIV-1 susceptibility of human foreskin. Foreskins from eight pediatric and six adult patients with (n = 3) and without (n = 11) histories of sexually transmitted disease were evaluated. Six cervical biopsies from HIV-1-seronegative women were included as controls. CD4(+) T cells, macrophages, and Langerhans' cells (LCs) were quantified using image analysis. Cells expressing HIV-1 co-receptors CCR5 and CXCR4 were quantified using immunofluorescence and image analysis. Foreskin biopsies were infected ex vivo in organotypic culture with HIV-1. HIV-1 DNA copies in foreskin and cervical mucosal tissue were compared and the infected cell phenotype was determined. Foreskin mucosa contained higher mean proportions of CD4(+) T cells (22.4%), macrophages (2.4%), and LCs (11.5%) in adults than in children (4.9%, 0.3%, and 6.2%, respectively) or in cervical mucosa (6.2%, 1.4%, and 1.5%, respectively). The highest proportions of CD4(+) T cells and LCs occurred in patients with a history of infection. Foreskin immune cells expressed predominantly the CCR5 HIV-1 co-receptor. Adult foreskin mucosa had greater susceptibility to infection with HIV(bal) than cervical mucosa or the external surface of foreskin tissue. Circumcision likely reduces risk of HIV-1 acquisition in men by decreasing HIV-1 target cells.

Cervix Uteri↗

Sustained ability for fibroblast outgrowth from stored neonatal foreskin: a model for studying mechanisms of fibroblast outgrowth.

Fibroblast cultures derived from neonatal foreskin explants have been an important model for understanding the basic mechanisms of fibroblast function and activity. Neonatal foreskin has been routinely used for establishing such fibroblast cultures in vitro. In general, tissue explants and fibroblast cultures are established from freshly harvested neonatal foreskin tissue. It is unknown whether prolonged storage of tissue, even in optimal growth media and conditions would still result in successful explant outgrowth. Specifically, no studies have properly examined the maximal duration of foreskin storage that can produce viable fibroblasts with normal growth and synthetic characteristics. We, therefore, set out to isolate and propagate fibroblast cultures from neonatal foreskin tissue that had been kept in complete culture media at 4 degrees C for various periods of time. We found that outgrowth and propagation of viable fibroblasts in vitro occurred with foreskin samples obtained within 24 days after surgical harvesting. The morphology, cellular proliferative capacity (measured by [3H]-thymidine uptake), steady state levels of alpha1(I) procollagen mRNA, and collagenous protein synthesis were comparable among fibroblast cultures derived from foreskin explants established 3 days (control) and up to 24 days (but not 38 days) after tissue harvesting. These studies demonstrate that viable and functional fibroblasts, with apparently similar in vitro characteristics, can be isolated and propagated from explants of neonatal foreskin tissue that have undergone prolonged storage. Moreover, these findings may be useful in understanding the lack of fibroblast growth in such conditions as found in delayed wound healing and aging.

Cell Division↗

Anti-Fas induces apoptosis and proliferation in human dermal fibroblasts: differences between foreskin and adult fibroblasts.

Apoptosis, or programmed cell death, is a naturally occurring process mediated by extracellular signals. We studied anti-Fas (CD95/Apo-1) antibody-induced apoptosis in cultured human foreskin and adult dermal fibroblasts. Induction of apoptosis was identified by fluorescence in situ DNA end-labeling. Anti-Fas antibody induced apoptosis in fibroblasts in a dose- and time-dependent manner. Adult dermal skin fibroblasts were more susceptible to anti-Fas antibody-induced apoptosis than foreskin fibroblasts, with 21-52% dead cells in different strains. In foreskin fibroblasts, anti-Fas antibody (1.0 microg/ml) predominantly induced proliferation ([3H]thymidine incorporation increased to 115-165% of control level) and only low levels of apoptotic cell death after 48 hours of treatment. No induction of proliferation by anti-Fas was found in the adult fibroblasts. Addition of tumor necrosis factor-alpha (TNF-alpha) slightly augmented the anti-Fas antibody-induced apoptosis in both cell types. When we examined the levels of Fas expression using flow cytometry, we found two- to threefold higher Fas expression in adult fibroblasts. C6-ceramide treatment, which induces Fas-independent apoptosis, gave similar levels of cell death in both foreskin and adult fibroblasts. No proliferation was observed in C6-ceramide-treated fibroblasts. Thus, this difference in apoptosis between adult dermal and foreskin fibroblasts appears to be related to the level of Fas expression. When clones of foreskin fibroblasts were examined, there was heterogeneity of anti-Fas antibody-induced apoptosis and proliferation in the cloned fibroblast subpopulations, but this was not correlated with differences in Fas expression. Alterations in fibroblast populations during the process of differentiation and aging may result from selective loss of apoptosis-susceptible populations.

Adult↗

Hormonal stimulation of tyrosinase activity in human foreskin organ cultures.

A human foreskin organ culture system has been developed to study the response of human skin to hormonal stimulation. Foreskins are maintained in culture on floating plastic supports which allows the epidermal surface to be exposed to air while the dermis is bathed in nutrient medium. Both black and white human foreskins can be maintained in organ culture for at least 1 wk with no change in the tissue structure or cell viability as determined by histochemical staining and by dopa reaction staining. Tyrosinase activity in both black and white human foreskin cultures decays markedly during the first 2 d of culture to a new steady state level which remains stable throughout the culture period. Both black and white foreskin cultures consistently demonstrate 2- to 10-fold increases in tyrosinase activity when treated with theophylline (1 mM). Approximately 90% of all skin cultures examined showed an increase in enzyme activity when treated with this phosphodiesterase inhibitor. Dibutyryl cAMP (0.1 mM) and [Nle4, D-phe7]-alpha MSH (10(-8) M), were also found to markedly stimulate tyrosinase activity in some skin cultures, whereas alpha-MSH and prostaglandin E1 produced only an inconsistent and small increase in the activity of the enzyme. Histamine (1 microM), vitamin D3 (1 microM), and retinoic acid (1 microM) failed to stimulate tyrosinase activity in either white or black foreskin cultures. This hormone-responsive organ culture system can be utilized to characterize the molecular processes responsible for the regulation of tyrosinase and pigmentation in human skin.

Alprostadil↗

Effect of topical steroid on non-retractile prepubertal foreskin by a prospective, randomized, double-blind study.

OBJECTIVE: The present study, conducted in Hong Kong, aimed to evaluate the effect of topical steroid in non-retractile prepubertal foreskin by a prospective, randomized, double-blind design. MATERIAL AND METHODS: 137 boys with non-retractile foreskin were randomized to betamethasone (n = 66) or placebo (n = 71 ) for 4 weeks with application of the cream twice daily. Non-responders to treatment were offered steroid treatment for a further 4 weeks. RESULTS: The mean pretreatment grade of the foreskin in the steroid and control groups was 5.08 +/- 0.66 and 4.97 +/- 0.70, respectively. At the 4-week follow-up, 49 of the former (74%) had a retractile foreskin (grade less than or equal to 3, mean 2.38 +/- 1.41). In contrast, only 31 of the control group (44%) had a retractile foreskin (less than or equal to 3, mean 3.55 +/- 1.55) (p < 0.001). Only 14 boys were circumcised because 43 of the remaining 57 boys had a retractile foreskin after 4 weeks of treatment. CONCLUSION: when treatment is necessary, application of topical steroid as a first line of treatment may avoid surgery in almost 90% of cases.

Administration, Topical↗

Treatment of phimosis with topical steroids and foreskin anatomy.

OBJECTIVES: To correlate topical steroidal treatment of stenosed foreskin with the different degrees of glans exposure and the length of time the ointment is applied. MATERIALS AND METHODS: We studied 95 patients with phimosis, divided according to the degree of foreskin retraction. Group A presented no foreskin retraction, group B presented exposure of only the urethral meatus, group C presented exposure of half of the glans, and group D presented exposure of the glans, which was incomplete because of preputial adherences to the coronal sulcus. Patients were submitted to application of 0.05% betamethasone ointment on the distal aspect of the prepuce twice daily for a minimum of 30 days and a maximum of 4 months. RESULTS: Of 95 patients, 10 (10.52%) abandoned the treatment and 15 patients in groups C and D were excluded from the study. Among the remaining 70 patients, only 4 patients (5.7%) in group A did not obtain adequate glans exposure after treatment. In group A (38 patients), fully retractable foreskins were obtained in 19 patients (50%) after 1 month of treatment. In group B (28 patients), fully retractable foreskins were obtained in 18 patients (64.2%) after 1 month. CONCLUSIONS: Treatment was successful in 94.2% of patients, irrespective of the type of foreskin anatomy. The improvement may require several months of treatment. Patients with impossibility of urethral meatus exposure present around 10% treatment failure.

Adolescent↗

[A method of one-stage correction of proximal hypospadia by deepithelialized foreskin graft].

The author proposes a modification of one-stage urethral plastic repair with cross-over graft from the foreskin according to Duckett for correction of proximal hypospadias with malformation or absence of the free trunkal part of the penis in well developed foreskin. From 1996 to 2001 one-stage operations were made in 82 boys at the age of 8 months to 15 years. Expanding of the cavernous bodies with loss of the urethral platform and plastic repair of a long urethral area were performed in 69 patients. These cases were most difficult for correction. Only plastic repair was made in the rest 13 children as their cavernous body deformation had been corrected previously. One-stage surgery of the urethra with dissection of the chorda was conducted by Hodgson-III in 13 patients, by modified Hodgson-III technique in 29 and by Duckett in 5 patients. Plastic repair with diagonal deepithelized graft from the foreskin was tried in 22 patients with underdeveloped volar surface of the penis. The modification consisted in cutting out the diagonal graft from the foreskin entoderm, forming a tube of it with uninterrupted suture, creation of the graft vascular pedicle by skeletization and deepithelization of the skin of the foreskin ectoderm and partially of the penis trunk, creation of a wide anastomosis of the formed tube with external opening of the urethra isolated by edge incision, mobilization of the glans penis wings by longitudinal incisions and creation of meatus on the top of the glans penis, mobilization of the foreskin and penis trunk tunica dartos with its placing from the dorsal surface on the ventral at both sides of the cavernous bodies. The treatment outcomes were followed up from 6 months to 3.5 years. Complications (stenosis of the external urethral opening, urethral fistulas and stenosis of the anastomosis zone) were observed in 13 (18.84%) patients. The proposed modification reduced the number of complications up to 13.63%, improved cosmetic and functional results.

Adolescent↗

The intromission function of the foreskin.

Masters and Johnson observed that the foreskin unrolled with intercourse. However, they overlooked a prior observation that intromission was thereby made easier. To evaluate this observation an artificial introitus was mounted on a scales. Repeated measurements showed a 10-fold reduction of force on entry with an initially unretracted foreskin as compared to entry with a retracted foreskin. For the foreskin to reduce the force required it must cover most of the glans when the penis is erect. This may occur only in humans. These observations mean that foreskin and prepuce can no longer be considered synonymous. Why the penises of humans and chimpanzees evolved so differently should be addressed in light of these findings.

Humans↗

Foreskin development before adolescence in 2149 schoolboys.

BACKGROUND: We examined the external genitalia of 2149 elementary schoolboys in the suburban area of Taichung in Taiwan for an understanding of foreskin development before adolescence. METHODS: The study's subjects comprised 692 first-grade boys, 725 fourth-grade boys, and 732 seventh-grade boys. The foreskin's condition was classified as: type I (normal prepuce), type II (adhesion of prepuce), type III (partial phimosis), type IV (phimosis) and type V (circumcised foreskin). Other abnormalities of the genitalia also were recorded. All of the examinations were performed by the same urologist. RESULTS: The incidence of type I foreskin was 8.2% in first-grade boys, 21.0% in fourth-grade boys, and 58.1% in seventh-grade boys. The incidence of type IV foreskin was 17.1% in first-grade boys, 9.7% in fourth-grade boys, and 1.2% in seventh-grade boys. Only one boy had balanoposthitis. Other abnormalities included inguinal hernia (n = 2), hydrocele (n = 12), cryptorchitism (n = 8), varicocele (n = 22), and subcoronal-type hypospadia (n = 1). CONCLUSIONS: Physiological phimosis declines with age. Most boys with phimosis in this study did not require treatment.

Adolescent↗

UV induction of cyclobutane thymine dimers in the DNA of cultured melanocytes from foreskin, common melanocytic nevi and dysplastic nevi.

We compared the induction of cyclobutane thymine dimers after exposure to 302 nm UV in foreskin-derived melanocytes and melanocytes from nevocellular nevi, as well as in melanocytes cultured from dysplastic nevi, precursor lesions of melanoma, derived from four, three and four individuals, respectively. Cyclobutane thymine dimers were quantified in situ by means of an immunofluorescence assay with a specific monoclonal antibody. A method was developed to compare separately performed experiments in a standardized manner. For melanocytes from each source, we demonstrated a linear relationship between UV dose and immunofluorescence. In nevocellular and dysplastic nevi, two subpopulations could be detected, distinguished by their nuclear size. Large nucleated nevocellular nevus cells were most susceptible to the induction of thymine dimers (49% higher induction compared to induction in foreskin melanocytes), while in normal-sized nuclei of these nevus cells the same induction of thymine dimers was found as in nuclei from foreskin melanocytes. In contrast, large nucleated dysplastic nevus melanocytes did not differ from the foreskin melanocytes, while normal-sized nuclei of dysplastic nevus cells showed a lower induction (32% lower induction than in foreskin melanocytes).

Cells, Cultured↗

[Foreskin retraction for phimosis of the newborn].

BACKGROUND: No guideline exists on how to treat boy's phimosis. We examined if retraction of the foreskin of the newborn boy's penis could make true phimosis become false phimosis. METHODS: We taught the mother to retract the foreskin and keep inside the foreskin clean. Exposure degree of glans by retraction of foreskin was defined in 7 grades, 0 (none) approximately III (middle) approximately VI (full). RESULTS: Of the 538 newborn examined, none had full exposure (VI). All of the 372 cases who continued the procedure, including 2 buried penis, gained full exposure (VI). Average time for full exposure according to the first degree of exposure was 2.94 months (0), 1.78 months (III), 1.22 months (V), 2.32 months average, respectively. No serious complications occurred. CONCLUSION: Retraction of the foreskin from the newborn period made all the true phimosis to be false phimosis and operative procedures became unnecessary.

Health Education↗

Non-retractile foreskin: a single center 13-year experience.

BACKGROUND: Non-retractile foreskin comprise a significant number of referrals by pediatricians and general practitioners to pediatric surgical centers. In attempts to find alternatives to widely practised circumcision, various procedures have been developed over the years in order to relieve the non-fibrotic narrowing of the foreskin. PATIENTS AND METHODS: In a 13-year period from 1984-1997, we treated 2554 patients with non-retractile foreskin at our center. Dorsal relieving incision was the technique of choice and was performed in 2177 patients, circumcision in 73 patients and preputial adhesiolysis was sufficient to retract the foreskin in 284 patients. RESULTS: Satisfactory esthetic results, an extremely low rate of postoperative complications (1.8%) with a recurrence rate of only 0.8% (18 patients) was observed in our series with dorsal relieving incision. CONCLUSIONS: Dorsal relieving incision operation was found to be a less invasive, safe and effective procedure for non-retractile foreskin not affected by extensive secondary scarring. This technique has fewer complications in comparison to circumcision and can be performed as an ambulatory procedure.

Adolescent↗

Human foreskin mast cell viability and functional activity is maintained ex vivo by coculture with fibroblasts.

The aim of the present study was to develop long-term culture conditions for foreskin-derived mast cells (HSMC) as we have previously done for rodent peritoneal mast cells (MC) and human lung-derived MC. HSMC were obtained by proteolytic treatment of foreskins from 8-day-old babies (4.8 +/- 2.0% purity) and seeded onto a confluent monolayer of human foreskin-derived fibroblasts (HF) in enriched culture medium. HSMC biochemical and functional properties were studied up to 8 days in these cocultures. Twenty-four hours after seeding the cell suspensions from the proteolytic-digested foreskins, all the cells which did not adhere to the HF were washed out. At this time point approximately 30% of the seeded HSMC were found to adhere to the HF monolayer. The only contaminating cells were endothelial cells (< 8%). Cocultured HSMC maintained their normal resting morphology and histamine content (3.1 +/- 0.7 pg/cell) up to 8 days in these cocultures. When challenged with compound 48/80 on Days 1, 2, 4, and 8 of coculture, HSMC released similar percentages of histamine which were comparable to the one released by freshly isolated HSMC in suspension (approximately 30%). Similarly, HSMC, sensitized with IgE antibodies and challenged at various time of coculture with anti-IgE antibodies, released throughout the experiment comparable percentages of this mediator (approximately 50%). Thus, coculture of HSMC with HF fibroblasts provides a suitable in vitro system for long-term studies on HSMC functional and biochemical properties in a microenvironment which mimics the physiologic one.

Cell Survival↗

Androgen receptor in human foreskin. II. Characterization of the receptor from hypospadiac tissue.

Hypospadias represents a spectrum of disorders known as androgen insensitivity syndromes, which are characterized by a nonresponsiveness of an androgen target tissue to the steroid. The basic defect in this disorder is unknown. This article presents results of studies of the androgen receptor with use of human foreskin from normal neonates undergoing circumcision and from patients undergoing urethroplasty necessitated by hypospadias. It is speculated that a defect in receptor level or function might explain this disorder. The androgen receptors from both normal and hypospadiac tissue were stabilized with a buffer containing 50 mM Tris hydrochloride, 1 mM ethylenediaminetetraacetic acid, 12 mM monothioglycerol, 10% (v/v) glycerol, and 10 mM sodium molybdate plus 1 mM phenylmethylsulfonylfluoride (pH 7.5). The receptors were characterized by Scatchard analysis, competitive binding assays, sedimentation analysis, molecular sieve chromatography, and isoelectric focusing techniques. Specific R 1881 binding to soluble proteins from normal human foreskin was shown to be high affinity (dissociation constant = 0.5 nM), low capacity (6 fmol/mg of protein), and steroid specific. Sedimentation analysis by sucrose density gradients demonstrated the 8S-to-4S shift from low- to high-salt treatments. The receptor from the foreskins of hypospadiac patients also contained androgen receptor in a concentration similar to that in the foreskins of normal persons. The affinity for steroid binding and sedimentation profiles or sucrose gradients of the androgen receptor between normal persons and hypospadiac patients were also similar. However, the androgen receptor from hypospadiac patients displayed different patterns of molecular sieve chromatography from those displayed by the receptor of normal persons. The reason for this difference is not known but may reflect a defective receptor and explain the basic mechanism of this disorder.

Androgen-Binding Protein↗