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PubMed2005

Sexual differentiation in three unconventional mammals: spotted hyenas, elephants and tammar wallabies.

The present review explores sexual differentiation in three non-conventional species: the spotted hyena, the elephant and the tammar wallaby, selected because of the natural challenges they present for contemporary understanding of sexual differentiation. According to the prevailing view of mammalian sexual differentiation, originally proposed by Alfred Jost, secretion of androgen and anti-Mullerian hormone (AMH) by the fetal testes during critical stages of development accounts for the full range of sexually dimorphic urogenital traits observed at birth. Jost's concept was subsequently expanded to encompass sexual differentiation of the brain and behavior. Although the central focus of this review involves urogenital development, we assume that the novel mechanisms described in this article have potentially significant implications for sexual differentiation of brain and behavior, a transposition with precedent in the history of this field. Contrary to the "specific" requirements of Jost's formulation, female spotted hyenas and elephants initially develop male-type external genitalia prior to gonadal differentiation. In addition, the administration of anti-androgens to pregnant female spotted hyenas does not prevent the formation of a scrotum, pseudoscrotum, penis or penile clitoris in the offspring of treated females, although it is not yet clear whether the creation of masculine genitalia involves other steroids or whether there is a genetic mechanism bypassing a hormonal mediator. Wallabies, where sexual differentiation occurs in the pouch after birth, provide the most conclusive evidence for direct genetic control of sexual dimorphism, with the scrotum developing only in males and the pouch and mammary glands only in females, before differentiation of the gonads. The development of the pouch and mammary gland in females and the scrotum in males is controlled by genes on the X chromosome. In keeping with the "expanded" version of Jost's formulation, secretion of androgens by the fetal testes provides the best current account of a broad array of sex differences in reproductive morphology and endocrinology of the spotted hyena, and androgens are essential for development of the prostate and penis of the wallaby. But the essential circulating androgen in the male wallaby is 5alpha androstanediol, locally converted in target tissues to DHT, while in the pregnant female hyena, androstenedione, secreted by the maternal ovary, is converted by the placenta to testosterone (and estradiol) and transferred to the developing fetus. Testicular testosterone certainly seems to be responsible for the behavioral phenomenon of musth in male elephants. Both spotted hyenas and elephants display matrilineal social organization, and, in both species, female genital morphology requires feminine cooperation for successful copulation. We conclude that not all aspects of sexual differentiation have been delegated to testicular hormones in these mammals. In addition, we suggest that research on urogenital development in these non-traditional species directs attention to processes that may well be operating during the sexual differentiation of morphology and behavior in more common laboratory mammals, albeit in less dramatic fashion.

Androgens↗
PubMed1998

Trypanosoma cruzi: compromise of reproductive system in acute murine infection.

Infection of isolated organs of the reproductive system by Trypanosoma cruzi has been described since Chagas' disease was first studied. A detailed histopathological analysis of mice acutely infected with T. cruzi CL strain showed colonization of male (preputial glands and skin, penis, testicular albuginea, epididymis, vas deferens, seminal vesicles, prostate, coagulative, bulbo urethral and urethral glands) and female (vagina, uterus, oviduct, ovary, mesovary, clitoris and mammary glands) structures of the reproductive system. The results presented herein demonstrated invasion of epithelial cells, pronounced colonization of the epididymis and male genital adnexa, but absence of parasitism in penile corpora cavernosa.

Animals↗
PubMed2002

Role of androgens in female genital sexual arousal: receptor expression, structure, and function.

OBJECTIVE: In women, androgens modulate the physiological function of many reproductive and sexual organs, including the ovaries, uterus, vagina, oviducts, clitoris, and mammary gland. In this article, we review the mechanisms of androgen action and discuss new data on the effects of androgens in vaginal and clitoral tissues. MAIN OUTCOME MEASURE(S): In this study, we characterized the androgen receptor expression in rabbit vaginal tissues from control and ovariectomized animals treated with or without androgen replacement therapy. We investigated the effects of androgen deprivation and replacement on the expression and activity of nitric oxide synthase and arginase and on vaginal smooth muscle contractility. RESULT(S): Androgens enhanced nitric oxide synthase activity and down-regulated arginase activity in proximal vagina. Estrogens down-regulated nitric oxide synthase activity and increased arginase activity in distal vagina. Androgens facilitated vaginal smooth muscle relaxation to electric field stimulation and vasoactive intestinal polypeptide, whereas estrogens attenuated vaginal tissue relaxation to electric field stimulation and to vasoactive intestinal polypeptide. CONCLUSION(S): These observations suggest that androgens may play an important role in modulating the physiology of vaginal tissue and contribute to female genital sexual arousal.

Androgens↗
PubMed1988

Early gender assignment in true hermaphroditism.

True hermaphroditism is a rare form of intersex anomaly where both male and female gonads are present. True hermaphrodites diagnosed in the past have been preferentially reared as males. However, based on the appearance of their external genitalia and the ability to reconstruct a functional genitourinary system, most of these children should be raised as girls. Between 1968 and 1987, we managed eight children with true hermaphroditism. The karyotypes were as follows: five 46XX, one 46XY, one 47XXY, and one 46XX/mosaic. Gonadal distribution was bilateral (two ovotestes) in two, lateral (testis and ovary) in two, and unilateral (ovotestis and ovary) in four. Seven patients were diagnosed shortly after birth. Six were raised as girls, two as boys. Based on a review of the relationship of external-internal genitalia, gonads, and karyotype of our own patients and those published by others, we believe that the appearance of the external genitalia alone allows a prompt and definitive gender assignment in infancy. This led us to develop a classification of external genitalia based on the following characteristics. Class I represents normal female genitalia, class II an enlarged clitoris, class III partially fused labioscrotal folds, class IV fused labioscrotal folds, class V a hypoplastic scrotum and penoscrotal hypospadias, and class VI represents normal male genitalia. We had two patients that were class II, two class III, three that were class IV, and one to IV should be raised as females; in class V, male gender assignment is preferable. This classification, based on the appearance of the external genitalia, allows a simple screening and prompt gender assignment in infants identified as true hermaphrodites.

Child↗
PubMed1998

Construction of a female urethra using the vaginal wall and a buttock flap: experience with 40 cases.

METHODS: From 1975 to 1996 a urethra was constructed using tubularized anterior vaginal wall covered with a buttock flap in 40 female patients in whom urinary incontinence was associated with a short or absent urethra. The underlying pathology included bilateral single ectopic ureters, cloacal malformation, urogenital sinus malformation, previous failed surgery of the urethra, severe trauma, myelodysplasia, female hypospadias, ectopic ureterocele with destruction of the urethra, congenital epispadias, bladder exstrophy, and previous hysterectomy and vaginectomy for clear cell carcinoma caused by intrauterine exposure to diethylstilbestrol. Other reconstructive procedures in these patients included bladder neck narrowing from above in 33 patients, ureteral reimplantation in 35, and bladder augmentation in 21. In the prone position, a tube of vaginal wall was used to create a urethra when it was absent or lengthen the urethra if it was too short. The neourethra was extended up to the base of the clitoris, using a multilayered closure of soft tissue over it distally with introital muscle and adjacent mucosa. The proximal neourethra was covered with a buttock flap. RESULTS: All patients were originally wet. Thirty-four are now dry. Four patients have minimal stress incontinence. Two patients have urinary diversions. The majority (n=25) void normally. Fourteen patients self-catheterize to empty their bladders. One patient wears an external appliance on the abdominal wall for collection of urine. Complications included: creating stress incontinence in one patient who had been previously dry by extracting a stone from the bladder, necrosis of a buttock flap from applying a tight perineal dressing, fistula requiring surgical closure in three patients, and slippage of the buttock flap in one patient. CONCLUSION: This operation is a useful method to correct diverse congenital and acquired pathology that causes incontinence in girls.

Adult↗
PubMed1999

Perineal hemangioma, anorectal malformation, and genital anomaly: a new association?

Two patients presented as full-term baby girls with anorectal and genital malformations with extensive perineal hemangiomas. The first patient had a vestibular anus with a perineal hemangioma involving the bladder, rectal, and vaginal walls. Skin ulcerations required a transverse loop colostomy for wound care. The vulva, urethral opening, and clitoris were deviated to the left, labia minora were absent, and the labia majora were abnormal. The second patient had an anus displaced anteriorly and deviated to the right. The external anal sphincter was hypertrophic on the left and atrophic on the right. Rectal examination showed agenesis of the right levator ani and a dentate line located at the skin level. She had a large perineal, sacral, vaginal, pararectal and retroperitoneal hemangioma and developed extensive skin ulcerations. She had only a hemiclitoris located to the left of the midline, near absence of labia minora, and hypertrophied labia majora. The urethra was displaced to the left and opened in the vestibule. Both patients had a spinal malformation (one with tethered cord and one with spina bifida) and a normal karyotype. Steroids and interferon allowed near-complete resolution of hemangiomas in both patients. The authors were impressed by the similarity of these two cases and could not find any previous description of this association.

Abnormalities, Multiple↗
PubMed2006

Female sexual dysfunction following vaginal surgery: a review.

PURPOSE: Depending on age it has been estimated that up to 40% of women have complaints of sexual problems, including decreased libido, vaginal dryness, pain with intercourse, decreased genital sensation and difficulty or inability to achieve orgasm. In this review we address the etiologies and incidence, evaluation and treatment of female sexual dysfunction following vaginal surgery for indications such as stress urinary incontinence and pelvic organ prolapse; anterior/posterior colporrhaphy, perineoplasty and vaginal vault prolapse. MATERIALS AND METHODS: Literature on the mechanisms by which vaginal surgery affects female sexual function are discussed along with related pathophysiology to potential causes. The anatomy, neurovascular supply of the clitoris and introitus, and intrapelvic nerve supply are discussed as related to vaginal surgery. Techniques to avoid neurovascular damage during pelvic floor surgery were corroborated by supporting literature. Literature regarding female sexual dysfunction following other procedures, such as vaginal hysterectomy, Martius flap interposition, and vesicovaginal and rectovaginal fistula repair were also discussed. RESULTS: Current literature does not support an association between vaginal length following vaginal surgery and sexual function. The proportion of women who are sexually active does not appear to be affected by vaginal surgery. Sling surgery for urinary incontinence does not appear to adversely affect overall sexual function, although individual parameters of sexual function scores may vary, eg a significant percent of women report pain during intercourse. Some patients experience improved overall sexual function due to complete relief from coital incontinence CONCLUSIONS: Symptomatic vaginal narrowing is rare even in women undergoing simultaneous posterior repair. Overall sexual satisfaction appears to be independent of therapy for urinary incontinence or prolapse. Data indicate that defect specific posterior colporrhaphy with the avoidance of levator ani plication may improve sexual function. The possible etiological factors for sexual dysfunction following vaginal surgery deserve further investigations.

Female↗
PubMed2006

Feminizing reconstructive surgery for ambiguous genitalia: the Leipzig experience.

PURPOSE: We report the results of feminizing reconstructive surgery for ambiguous genitalia with regard to the degree of virilization according to Prader and the long-term outcome with special emphasis on sexual intercourse. MATERIALS AND METHODS: Patients 16 to 46 years old with CAH (41) and MPH (17) were followed continuously by an interdisciplinary team that provided standardized hormone substitution and reconstructive surgery. More virilized genitalia were treated using a 2-stage procedure. RESULTS: Of patients with CAH no surgery and clitoris reduction were done in 4 and 2 (Prader I and II), no surgery, a 1-stage and a 2-stage procedure were done in 2, 3 and 4 (Prader III), a 2-stage procedure, a 1-stage procedure and surgery for fistula were done in 16, 4 and 2, respectively, while 1 refused surgery (Prader IV), and a 2-stage procedure was done in 5, including pull-through vaginoplasty in 2 (Prader V). Of patients with MPH no surgery was done in 6 (Prader I and II), a 1-stage procedure and a 2-stage procedure were done in 3 and 1 (Prader III), respectively, and a 2-stage procedure was done in 6, while 1 refused surgery (Prader IV). Revision vaginoplasties were necessary in 7 patients (12.1%) because of scar stenosis in those who underwent 1-stage as well as 2-stage procedures. None of our patients required reconstructive surgery to create a neovagina. Of the 58 patients 32 achieved sexual intercourse and in 17 the postoperative result would allow sexual intercourse, while in 3 the possibility of sexual intercourse is uncertain. For 3 patients sexual intercourse would not be possible since feminizing reconstructive surgery was refused. One patient could not be followed. CONCLUSIONS: Two-stage surgery leads to a favorable outcome in patients with CAH and MPH, and virilized genitalia (Prader IV and V).

Adolescent↗
PubMed2001

1-Stage feminizing genitoplasty: 8 years of experience with 49 cases.

PURPOSE: We retrospectively evaluated the results of a modified technique for 1-stage feminizing genitoplasty in children with congenital adrenal hyperplasia (CAH) and other rare intersex conditions. MATERIALS AND METHODS: Between 1991 and 1998, 47 infants and 2 adolescents underwent 1-stage feminizing genitoplasty at our hospital. Of the patients 44 had CAH, 2 had the partial androgen insensitivity syndrome and 3 were true hermaphrodites. In 3 patients we used the Passerini-Glazel technique, while in 46 our technique of feminizing genitoplasty was used, which consists of maximal mobilization of the urogenital sinus en bloc including the vagina and urethra via the perineal approach. Two lateral plates built from dorsal split phallic and preputial skin together with the dorsal split urogenital sinus are used to construct the vaginal introitus and labia minora, and the scrotal folds are used to construct the labia majora. Reduction clitoroplasty is done according to the technique of Kogan et al. Mean age plus or minus standard deviation was 0.9 +/- 0.3 years of the patients with CAH and 13 +/- 2.3 of the remainder. Preoperative information, including status of the internal genitalia, anatomical length of the vagina site of communication between the vagina and urogenital sinus, in relation to the pelvic floor, was obtained by transabdominal pelvic ultrasound. RESULTS: Operating time ranged between 120 and 180 minutes, average hospitalization period was 4 to 5 days and mean followup was 4.7 +/- 2.6 years. Preoperative ultrasound provided the correct data regarding the vaginal and internal genitalia anatomy in all cases, and the exact communication site between the vagina and urogenital sinus was demonstrated in 93%. Complications consisted of intraoperative rectal injury in 1 case and mild wound infection of the buttocks area in 3. In 1 case total clitoris loss was observed. All patients who underwent modified genitoplasty have had successful cosmetic and early functional results. Two patients presented with repeat clitoromegalia due to inadequate adrenal suppression. CONCLUSIONS: Our adapted technique of 1-stage feminizing genitoplasty provides good cosmetic and functional results. The functional results of this operation should be reevaluated after puberty and in adulthood.

Adolescent↗
PubMed1989

Prenatal fetal adrenal suppression following in utero diagnosis of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency can result in marked virilization of the external genitalia of affected female subjects. Theoretically, suppression of the fetal pituitary-adrenal axis with glucocorticoid during gestational weeks 9 to 17 should prevent the development of ambiguous genitalia in the female fetus. Prenatal diagnosis of congenital adrenal hyperplasia can be made on elevated amniotic fluid 17-hydroxyprogesterone and adrenal androgen concentrations, and HLA typing of cultured amniotic fluid cells. However, these tests cannot be completed before 16 to 17 weeks of gestation, and maternal therapy would have to be instituted before the exact genetic status of the fetus is known. Chorionic villus sampling during the first trimester provides an alternative to second trimester diagnosis in patients who are at risk for bearing offspring with congenital adrenal hyperplasia. We report the use of dexamethasone suppression at 8 weeks of gestation in a 34-year-old woman whose son had congenital adrenal hyperplasia due to severe salt-losing 21-hydroxylase deficiency and whose biopsy revealed a 46XX chromosomal pattern. Cultured cells from the biopsy confirmed the fetus to be of identical HLA haplotype to the previous affected sibling. At 41 weeks the patient delivered a female neonate with minimal prominence of the clitoris, mildly rugated labia, a single perineal opening and minimal posterior labial fusion. Postnatal tapering of maternal steroids was performed with no long-term sequelae.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Persistent cloaca and phallic urethra.

During the last 8 years 54 children with a persistent cloaca have been treated by one of us (A. P.). The most common associated anomalies involved the urinary tract, with renal agenesis, renal dysplasia, vesicoureteral reflux and megaureter encountered most frequently. Four patients demonstrated the rare entity of an opening at the tip of a pseudophallus and 2 also had an accessory urethra in association with the cloacal malformation. These children exhibited some form of masculinization of the external genitalia with the accessory urethra or cloacal channel assuming a phallic position in an enlarged clitoris. No adrenal, metabolic or chromosomal abnormalities were detected and virilization was limited to the genitalia. These cases illustrate the greater predilection of these patients to more complex congenital malformations than patients with an isolated cloaca. The posterior sagittal approach has been used effectively for repair of these congenital malformations.

Abnormalities, Multiple↗
PubMed1983

Feminizing genitoplasty: a synthesis.

The female child with the adrenogenital syndrome is subject to a variable degree of masculinization. Surgery should be directed to 3 goals: 1) removing the corpora and preserving the glans with its innervation to create a clitoris with normal sensation, 2) creating a normal-appearing introitus by fashioning labia minora from phallic skin and foreskin, and 3) vaginoplasty to provide an adequate opening for the vagina onto the perineum. The entire repair may be completed before the age of 6 months unless the vagina enters the urogenital sinus at a high level in which case vaginoplasty should be delayed until the child is older. The evolution of this operative approach is described and the details of the operative technique are presented.

Adrenal Hyperplasia, Congenital↗
PubMed1982

Leydig cell hypogenesis: a rare cause of male pseudohermaphroditism and a pathological model for the understanding of normal sexual differentiation.

We describe a patient who presented for treatment of primary amenorrhea and was found to have male pseudohermaphroditism due to Leydig cell hypogenesis. This rare disorder is characterized by ambiguous genitalia with a normal clitoris, labioscrotal folds, a urogenital sinus and inguinal or intra-abdominal testes microscopically devoid of mature Leydig cells. The diagnosis is made biochemically by the presence of low testosterone and estradiol values with elevated luteinizing hormone levels in the absence of other significant hormonal changes. The clinical and laboratory features of this disorder offer support for human developmental concepts derived from animal models.

Adult↗
PubMed1980

Construction of female urethra from vaginal wall and a perineal flap.

Five incontinent girls between 4 and 18 years old were made continent by constructing in each case a long extension of the urethra up to the clitoris. Previous operations at the proximal end of the urethra, to narrow the bladder neck, had not achieved continence. Lengthening the urethra was accomplished by tubularizing the anterior vaginal wall and covering that with a generous pedicle flap from the perineum. The base of the pedicle flap was divided later, restoring the introitus to a normal appearance. Of the 5 patients 3 had the underlying problem of ureteral ectopia with congenital deficiency of the urethra and the bladder neck, 1 had a marked degree of female hypospadias with absence of the distal urethra and in 1 the cause for incontinence was extensive internal urethrotomy during early childhood. This procedure should be applicable to certain difficult cases of incontinence in pediatric and adult patients.

Adolescent↗
PubMed1997

Short-term effects of topical testosterone in vulvar lichen sclerosus.

OBJECTIVE: To evaluate the systemic and therapeutic effect of topical testosterone treatment in vulvar lichen sclerosus. METHODS: This prospective clinical, single-arm study included ten postmenopausal women with vulvar lichen sclerosus. Testosterone propionate (0.04 g daily) was administered topically for 4 weeks. Serum androgens (testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate) were determined before and after 4 weeks of treatment, and vulvodynia was evaluated by a horizontal visual analogue scale. RESULTS: Serum levels of total testosterone increased in all patients (P < .01) and exceeded normal range in eight of ten women. Vulvodynia improved in nine of ten patients (paired t test: P < .01). Four of ten patients showed clinical signs of hyperandrogenism (enlargement of the clitoris, alterations of the voice, increase in libido) after 4 weeks of treatment. The only patient without subjective improvement had elevated basal serum androgen levels and showed clinical signs of hyperandrogenism before therapy. CONCLUSION: Topical testosterone is effective in normoandrogenic women with lichen sclerosus. Androgen status should be evaluated before treatment, and dosage should be individualized to avoid virilization and metabolic side effects. Because there is a marked systemic effect, clinical controls and a follow-up with evaluation of serum testosterone levels are recommended. Other steroids should be included in therapeutic decisions.

Administration, Topical↗
PubMed1998

Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia.

The histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized. Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied. Paraffin sections of vulvar LS, and three controls groups (acute scars, normal vulva, and vulvar lichen simplex chronicus [LSC]) were investigated with a panel of seven tissue markers and for DNA content in areas without vulvar intraepithelial neoplasia (VIN). All published cases to date of vulvar LS associated with SCC were reviewed. Of the cohort of symptomatic vulvar LS patients (mean/median age, 60 years), 9% developed VIN lesions and 21% invasive SCC; symptomatic LS preceded the carcinoma by a mean of 4 years (range, 1 to 23 years). Second and third primary tumors developed in three of these patients. Of the series of 60 patients presenting with vulvar SCCa, the clinical setting and histological features of SCCs associated with LS were significantly distinctive compared with SCCas without LS: SCCs associated with LS occurred in an older age-group (74 v 65 years; P = .01), were located on the clitoris (41% v 5%; P = .003), were of conventional SCCa type (85% v 57%; P = .02), were associated with a prominent fibromyxoid stromal response (46% v 10%; P = .004), were not associated with VIN 3 (SCC in situ) (5% v 67%; P = .02) and diffusely expressed tumor suppressor gene product p53 (43% v 19%; P = .01) and cytokine TGF-beta (33% v 9%; P = .05). The epidermis of vulvar LS was similar to that of acute scars and differed significantly compared with normal vulva with respect to keratinocytic expression of markers to keratin AE 1, involucrin and filaggrin, epidermal thickness (0.13 mm [LS] v 0.05 mm [normal]; P < .03), and proliferative index by PCNA and Mib-1 labeling (53/60 [LS] v 15/19 [normal] per 200 basal cells [bc]; P < .003). Vulvar LS showed significantly higher expression of p53 than all three control groups (80 [LS] v 3 [normal]/44 [acute scar]/28 [LSC] per 200 bc; P < .008), and aneuploidy (33% v diploid controls) in the absence of VIN. Comparing LS with and without associated SCCa found significant increases in age of patients (74 v 66 years; P = .001), and DNA aneuploidy (52% v 11%; P = .0001) and no differences in epidermal thickness, sclerotic thickness, proliferative index, or p53 expression. However, those cases of LS with an aneuploid DNA content showed significantly elevated p53 expression (88 v 60/200 bc; P = .01) and epidermal thickness (0.16 v 0.11 mm; P = .005) compared with LS with a diploid DNA content. Review of published cases supports an association between LS and vulvar SCC. The phenomenon of chronic inflammation and scarring giving rise to carcinoma has been well documented. Vulvar lichen sclerosus (LS) is an inflammatory dermatosis characterized by clinicopathologic persistence and hypocellular fibrosis (sclerosis). A subset of vulvar SCCs is significantly associated with the presence of LS and diffusely express the p53 gene product. Keratinocytes affected by LS show a proliferative phenotype and can exhibit markers of neoplastic progression such as increased p53 expression and DNA aneuploidy. As a chronic scarring inflammatory dermatosis, vulvar LS could act as both "initiator and promoter" of carcinogenesis, explaining the frequent coexistence of these diseases. Because keratinocytes of LS significantly express tumor suppressor gene p53 protein, the p53 gene may be involved early in this proposed pathway of carcinogenesis.

Adult↗
PubMed2002

Ultrasonic measurements of second and third trimester fetuses to predict gestational age and date of parturition in captive and wild spotted hyenas Crocuta crocuta.

Parturition in spotted hyenas (Crocuta crocuta) is a fascinating event to witness, as females of this species are highly masculinized and give birth through a penis-like clitoris. Furthermore, shortly after birth, a high rate of aggression occurs between littermates that can sometimes end in siblicide. To study these events thoroughly, an accurate estimate of the date of parturition is necessary. To this end, we performed transabdominal ultrasounds every 20-30 days in five captive spotted hyenas of known gestational age, beginning approximately 30 days after mating. We measured the femur length (FL), abdominal circumference (AC), and biparietal diameter (BPD) of eight fetuses from Days 42 to 100 of their 110 days of gestation. FL proved to be the most effective measurement, as it correlated well with gestational age and was easy to obtain consistently. The relationship between estimated gestational age (EGA) and FL is described by the equation: [EGA = 37.3 + (14.0 x FL)]. AC also correlated well with EGA, but was more difficult to measure than FL. Measuring BPD became increasingly difficult as pregnancies advanced beyond 70 days of gestation. Because gestational age is often not known in captive and free-ranging spotted hyenas, measuring fetal FL ultrasonographically is a rapid and reliable way to determine an approximate date of parturition. This technique proved invaluable when used to track and monitor a free-ranging spotted hyena during the days just before and after parturition.

Abdomen↗
PubMed1998

Long-term disease-free survival following surgery and active specific immunotherapy with allogeneic vaccine in a patient with high-risk malignant melanoma of the vulva.

Vulvar malignant melanoma with deep vertical penetration of the tumor and involvement of regional lymph nodes carries a very poor prognosis. The case of a 25-year-old woman with a history of a Breslow depth 6.0 mm and Clark Level IV primary vulvar malignant melanoma, involving the anterior part of the left labium major, 1 cm from the clitoris, is reported. The patient had undergone a left radical hemivulvectomy and bilateral groin dissection. There were two of thirteen superficial left groin nodes containing metastatic melanoma. The patient had been treated postoperatively with an allogeneic specific anti-melanoma vaccine in combination with high-dose cimetidine and has survived without disease for more than five years. To the best of our knowledge this is the first case report in the literature of active specific immunotherapy with allogeneic vaccine in vulvar malignant melanoma. This case illustrates that the behavior of malignant melanoma, including vulvar malignant melanoma, is unpredictable and active specific immunotherapy with allogeneic vaccine may have a role in the postoperative treatment of high risk vulvar malignant melanoma.

Adult↗