The therapeutic benefits of combined MCT with cyclophosphamide plus celecoxib on mammary adenocarcinomas together with its very low toxicity profile warrant further study in an attempt to make the translation into the clinic.
Background: Hermaphroditism is a rare congenital disease that causes ambiguous sexual features. True hermaphrodites have testicular and ovarian tissue, whereas pseudohermaphrodites have only one type of gonadal tissue, genitalia, but secondary characteristics of the opposite sex. Pseudohermaphrodites are classified as male or female according to their gonads. Treatment of pseudohermaphroditism consists of surgical removal of the gonads including reconstruction of abnormal genitalia, especially if the urethra is involved. Therefore, the objective of this report is to describe a case of a male pseudohermaphrodite in a dog treated with clitoridectomy with urethrostomy.Case: A 7-month-old, mixed-breed dog was referred due to the presence of a flaccid structure similar to a small penis, containing an os clitoris, bulbourethral glands, and urethra protruding from the vulva. Physical examination, complete blood count and serum biochemistry were within normal ranges. Hormonal levels of estradiol, testosterone, and progesterone were 56.39 pg/mL, 127.9 ng/mL, and 0.892 ng/mL, respectively. The abdominal ultrasound and posteriorly the exploratory celiotomy found a normal size prostate and two round organs resembling testicles connected to a uterus-like tubular structure. The patient underwent surgical abdominal exploration that confirmed the ultrasonographic findings and led to gonadohysterectomy. Also, clitoridectomy and urethrostomy were performed to excise the protruded structure and maintain normal urethral patency. The histopathological examination of the clitoris and penis confirmed it was a male genital organ, however, the abdominal structures were compatible with the testicles, epididymis, uterus, and even a broad ligament. These organs are normally found in cases of male pseudohermaphroditism. The testicles were histologically composed of regular seminiferous tubules, single layer Sertoli cells but there were no spermatogenic cells. After ten months of follow-up, the patient was alive, without urination impairment or any other clinical signs.Discussion: The animal presented the protrusion of the penile structure as the sole clinical sign. The reproductive system had a female origin, been possible its masculinization due to high testosterone concentration that induced the development of Wolff ducts, resulting in the formation of the epididymis, deferent ducts, and seminal vesicles. In these cases, it led to an enlarged clitoris. The patient described had hormonal levels compatible with a neutered male/female or a female in anestrus. The clinical signs become evident as the clitoris gets hypertrophied increasing the sensibility, resulting in constant licking of the mucosa, chronic inflammation, and mucopurulent discharge. This patient was diagnosed with male pseudohermaphroditism as it had cryptorchid male gonads along with the uterus and external genitalia of a female dog but containing traces of male genitals such as the os clitoris. Surgery is indicated when there are clinical signs or when the clitoris had an os clitoris or urethra due to an intersex abnormality. The surgical resection of the external male genitalia associated with the excision of the internal reproductive tract treated while preserving the urethra in this animal. Clitorectomy is a simple technique and creates a normal female anatomy ending the clinical signs of the exposed clitoris and improving the quality of life.Clitoridectomy and Urethrostomy in a Pseudohermaphrodite Dog
Metronomic chemotherapy (MCT) refers to the chronic, equally spaced, delivery of low doses of different chemotherapeutic drugs, without extended interruptions. CY, administered in low dose, is able to modulate the immune response. It can also reduce tumor angiogenesis, like the COX-2 inhibitor CEL does. We have already demonstrated that the administration, as an intervention strategy, of metronomic CY + CEL in M-406 and M-234p mammary adenocarcinomas-bearing mice inhibited tumor growth, increasing the survival rate. Our present aim was to study the mechanism by which that therapeutic effect was achieved. CBi and Balb/c inbred mice were s.c. challenged on day 0 with M-406 or M-234p mammary tumors, respectively, and treated from day 8 (M-406) and 5 (M-234p) on with: I) no further treatment (controls); II) CY in the drinking water (25-30 mg/kg body weight/day); III) CEL (30 mg/kg p.o.), five times/week; IV) Treated as II + III. Blood samples were taken on days 0, 20 (M-406) and 30 (M-324p) to evaluate VEGF serum level determined by ELISA and the % of circulating regulatory T cells (Tregs) by flow cytometry. The same tumor challenges and therapeutic schedules were performed in nude mice. Tumors were excised on days 20 and 30 for M-406 and M-234p, respectively, fixed and paraffin embedded for detection by immunohistochemistry of CD34 and Ki67 molecules. The VEGF serum level of M-406-bearing control animals (group I) was, on day 20, significantly higher than that measured on day 0 (p<0,001), while groups II, III y IV showed, on day 20, lower values than group I (p<0.01) in the same day, and similar than those on day 0. The % of CD4+ CD25+ Foxp3+ Treg cells in serum showed no differences between days 0 and 20 in all the experimental groups. The antitumoral effect of MCT was the same in euthymic and athymic mice. Immunohistochemistry for CD34 showed slight differences between control and treated animals that were not significant. Also, the staining for the proliferation marker Ki67 did not evinced differences among the experimental groups. The results obtained with M-234p tumor model were similar to those of M-406. In conclusion, the antitumor effect of MCT with CY plus CEL in mammary tumor models would be achieved, at least in part, by the inhibition of tumor angiogenesis, without modulation of the antitumor immune response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3655.
Background: The congenital flexural deformity is common in cattle, often affecting the metacarpophalangeal joint of the thoracic limbs. The deformity may be mild, moderate, or severe, and the therapy depends on the limb's degree of flexion and the affected joint. In severe deformities, tenotomy of the flexor tendons and desmotomy of the suspensor ligament is recommended. However, this surgical technique may not be sufficient to promote limb extension, and other interventions may be necessary. Thus, the purpose of this report is to describe a technique to correct severe flexural deformities of the metacarpophalangeal joint in calves.Case: A three-month-old, female, Dutch-bred calf weighing 46 kg was referred for treatment of congenital flexural deformity. On attendance, the patient presented severe deformity in the right thoracic limb and mild in the left thoracic limb both at the height of the metacarpophalangeal joints. During palpation it was possible to notice that the flexor tendons were contracted in both limbs. Radiographic exams were performed to rule out the presence of other diseases, confirming the diagnosis of flexural deformity. The patient was referred to surgery to correct the anatomical anomaly. The animal was submitted to general anesthesia and placed in right lateral decubitus. In the left thoracic limb, an incision was made in the medial region of the metacarpal bone, the tissues were divulsioned until the superficial digital and deep digital flexor tendons were exposed; these structures were sectioned with a scalpel, and the limb was extended, returning to the standard anatomical position. In the right thoracic limb, the same procedure was performed, but during the limb extension test, we observed that the limb remained flexed, we then followed with a second incision and section of the deep digital flexor tendon in the palmar region at the middle phalanx of the lateral and medial digits, with this procedure, the limb extended further. Nevertheless, the procedure was not enough to solve the problem in the right thoracic limb, and the patient needed a second surgical intervention, in which we performed again tenotomy of the flexor tendons and desmotomy of the digital annular, crossed sesamoid, and interdigital phalangiosamoid ligaments, associated to the capsule opening of the capsule from the affected right metacarpophalangeal joint. After this surgery, the patient recovered to the normal anatomical position of the right thoracic limb. The procedures were efficient in achieving the normality of both affected limbs, and the patient recovered without postoperative complications.Discussion: In severe flexural deformities of the metacarpophalangeal joint in bovines, the fetlock's flexor tendons and suspensory ligament are implicated in the limb contracture. For these cases the chosen treatment is surgery with sequential sectioning of the flexor tendons and the suspensory ligament until the extension of the flexed limb occurs. Although there are reports that confirm the efficacy of this technique, there are cases in which other anatomic structures are involved in the limb contracture. In addition, the desmotomy and tenotomy techniques are not enough to achieve the normality of the affected joint, with the limb remaining flexed, leading to euthanasia of the patient in some cases. In cattle, few reports demonstrate possible techniques for severe contractures of the metacarpophalangeal joint, requiring further studies and new techniques to achieve recovery of these patients. Keywords: bovine, congenital, anatomical anomaly, contracture, tendon, fetlock.Descritores: bovinos, congênita, anomalia anatômica, contratura, tendão, boleto.Título: Correção de deformidade flexural da articulação metacarpofalangeana em uma bezerra
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