Clinical, ultrasonographic and pathological features following unilateral vasectomy in rams

The effects of vasectomy on testes and related structures of animal species and men are largely disputable. These possible effects were studied in the ram, an established experimental animal model used to investigate genitalia pathophysiology. In each of five rams, vasectomy in the left spermatic cord was carried out; subsequently, the clinical and ultrasonographic features were monitored up to 12 months post-operatively. The rams were sequentially euthanatized 1, 3, 6, 9 and 12 months post-operatively; gross- and histo-pathological examination of their testes and related structures were carried out. Four of the five rams developed sperm granulomas at the proximal to the testis end of vas deferens or/and at the tail of the epididymis; these were palpable from the first and the third month after vasectomy, respectively. Ultrasonographic findings on the vasectomy side were increased size and echogenicity of the epididymal tail, as well as anechoic areas, representing sperm granulomas, visible in the epididymal tail 1 week after vasectomy and in the proximal to the testis end of vas deferens 4 weeks after vasectomy. Gross pathological findings were limited on the vasectomy side and included adhesions between the parietal and the visceral vaginal tunic, enlarged and firm epididymal tail and presence of sperm granulomas at the epididymal tail or/and at the proximal to the testis end of vas deferens; the granulomas contained creamy material. Histopathological changes were observed mainly in the epididymal tails, consisting of a central mass of spermatozoa, surrounded by a layer of macrophages, surrounded in turn by loose vascular connective tissue rich in lymphocytes and plasma cells. With the exception of signs of mild hypospermatogenesis observed in one ram euthanatized 9 months after surgery, and of a slight increase in seminiferous tubule diameter and in seminiferous epithelium height in the rams euthanatized 6 and 9 months after surgery, which are both findings of no clinical importance, no clinical, ultrasonographic, gross- or other histo-pathological changes were observed in the testicular parenchyma during a 12-month post-operative period. These results demonstrate that vasectomy has little if any detrimental effect on the morphologic characteristics of the spermatogenesis in rams.     

貂、狐、貉群犬瘟热临床及病理学研究

对2006年6～10月山东、河北等地区的部分毛皮动物养殖场发生疑似犬瘟热的疫情进行了流行病学、临床症状以及剖检病变观察和分析,对采集的病料进行了细菌分离鉴定、病毒特异性核酸检测,并选取肝、脾、肺、心、脑、膀胱和胃进行了病理组织学检查.结果表明,这起疫情主要是由携带CDV的貉、貂调运而促进病毒传播感染引起.发病动物剖检病变以全身脏器出血性变化为特征,病情及病变严重程度依次为貉＞狐狸＞水貂.病理学变化特征为肺泡壁增厚,大量炎性细胞浸润,且在脱落肺泡上皮细胞、膀胱上皮细胞胞浆内偶见嗜酸性的球形包涵体,支气管上皮变形、坏死、脱落,淋巴细胞浸润;非化脓性脱髓鞘性脑炎;脾脏、肾脏、心脏、肝脏、胃和肠道有不同程度出血、坏死等病变.通过对发病狐、貉、貂的肺、肝、脑、膀胱等脏器病理学比较,在病变程度上水貂与狐狸、貉有差异.但是同一种动物,依病程、病型及有无并发症等因素,病理学变化也存在差异.     

Androgen receptors and partial androgen insensitivity in male pseudohermaphroditism

Male pseudohermaphroditism can occur either as a result of inadequate fetal androgen secretion or ineffective androgen action. Partial androgen insensitivity syndrome is related to a decrease in the binding capacity of target cells androgen receptors. However, the biochemical expression of these syndromes is variable: although a low concentration of androgen receptors is observed in 75% of the cases, a normal binding capacity is sometimes reported. If the presence of androgen receptors is necessary for hormonal action, it is not sufficient since the receptor has to conserve its functional integrity. Several qualitative abnormalities of the androgen receptor have been described and could thus explain the disturbance in the androgen mechanism of action. The study of androgen-dependent proteins and other androgen-receptor "markers" should offer the clinician a better management of partial androgen insensitivity and allow, in amniotic or trophoblastic cells, a prenatal diagnosis of androgen resistance in high-risk families.     

H-Y antigen-positive male pseudohermaphroditism with 45,X/46,XYq-mosaicism

Summary A 42-year-old male had short stature, microphallus, hypospadias, a bifid scrotum, abdominal undifferentiated testes, a uterus, bilateral fallopian tubes, and 45,X/46,XYq-mosaicism in his blood, skin, and germinal tissue and tissue surrounding the testes as determined by means of G-, Q-, and C-banding. An H-Y antigen assay on skin fibroblasts was positive, indicating that the locus for this antigen is not located in the brightly fluorescent region of the Y chromosome.     

Ectopic dioctophymosis in a dog – Clinical,diagnostic and pathological challenges of a silent disease

A 9-month old, female, stray dog was rescued and conducted to a university veterinary hospital. Moderate anemia was observed and abdominal ultrasound revealed pancreatitis. Right kidney was not visualized due to intestinal gas. Urinalysis was normal. Castration was performed three weeks later. Before discharge, abdominal ultrasound was performed for internal sutures examination. A cyst-like structure was present in the right retroperitoneal space with what appeared to be tubular worms inside it, not observed in previous evaluation. An ectopic dioctophymosis diagnosis was made. Two female Dioctophyme renale were surgically removed from the structure. Right kidney was hyperemic but not removed. No sign of peritonitis was observed. The dog recovered well. Laboratory follow-up showed no abnormalities a year after the episode and Doppler ultrasound revealed a mild right nephropathy. This is the first canine ectopic dioctophymosis case with only an abdominal cyst-like structure containing viable nematodes, successfully treated. It represents the rarity and difficulties in diagnosing ectopic dioctophymosis even in enzootic locations, highlighting the importance of ultrasonographic screening for such silent, potentially zoonotic disease.     

Aniridia,male pseudohermaphroditism,gonadoblastoma, mental retardation,and del 11p13

Summary A 20-month-old male patient was referred because of severe growth and mental retardation, bilateral glaucoma, hypospadias, and cryptorchidism. Karyotyping revealed a de novo complex three-chromosome rearrangement as well as deletion of band 11p13:46,XY,t(4;7;15)(q212;p14;q26),del(11) (p13p14). Trabeculectomia revealed bilateral aniridia. Surgery on the genitalia revealed male pseudohermaphroditism and bilateral gonadoblastoma. The kidneys were normal. A deficiency in catalase (CAT) activity allowed the regional assignment of the CAT gene to band 11p13.     

Clinical features,treatment and genetic background of Treacher Collins syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development. The major features of the disease include midface hypoplasia, micrognathia, microtia, conductive hearing loss and cleft palate. Current procedures of surgical treatment of TCS are discussed and novel findings concerning the genetic background of TCS are described. The TCS locus has been mapped to chromosome 5q31.3-32. The TCOF1 gene contains 26 exons and encodes a 1411 amino acid protein named treacle. In the TCOF1 gene 51 mutations have been identified. Most of these mutations are insertions or deletions, which result in an introduction of a premature termination codon into the reading frame. Mutational spectra support the hypothesis that TCS results from haploinsufficiency of treacle.     

Phenotypic feminization in a genetic male dog caused by nonfunctional androgen receptors

A dog raised as a female pup did not have utero-ovarian structures when ovariohysterectomy was attempted at 6 mo of age. Three months later, the dog exhibited male-like behavior, and 2 symmetrical testicular-shaped structures arose bilateral to the vulva. Intersex cases such as this one may involve chromosomal abnormalities, defects in testicular secretions or androgen insensitivity in tissues of the sex accessories. Serum concentrations of testosterone and dihydrotestosterone were measured in the intersex and in intact normal male (control; n=7) dogs. In addition, 5alpha-reductase enzyme activity was determined in the gonadal tissue of the intersex dog and control dogs. Androgen receptors were studied in cultured fibroblasts from the genital skin of the intersex and control dogs. The cytogenetic studies identified the animal's karyotype to be 78 XY. All complete cells from the gonadal tissue showed an XY sex chromosome complement. Serum testosterone concentrations before and after challenge with hCG were not different between the intersex and control dogs (6.2 vs 5.72 +/- 1.8 ng/ml and 9.5 vs 8.69 +/- 2.39 ng/ml before and after hCG challenge, respectively). Similarly serum dihydrotestosterone concentrations were not different between the intersex and control dogs before and after challenge with hCG (158 vs 162 +/- 1.4 pg/ml and 270 vs 278.71 +/- 45.98 pg/ml before and after hCG challenge, respectively). The 5alpha-reductase enzyme activity of the gonads was not different between the intersex and control dogs (105 pmol/h/mg protein vs 110 +/- 2.4 pmol/h/mg protein). The Bmax values of binding in the control dogs fibroblast strains were 25 +/- 3.5 fmol/mg protein. However, specific binding of dihydrotestosterone was virtually undetectable in the fibroblasts cultured from the intersex dog. These results exclude chromosomal abnormalities and deficient secretion of testosterone and dihydrotestosterone as causative factors. Because fibroblasts cultured from genital skin lacked any ability to specifically bind dihydrotestosterone, it is suggested that nonfunctional androgen receptors in some tissues of the sex accessories contributed to the feminine phenotype of this particular dog.     

Clinical and molecular genetic features of ARC syndrome

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (MIM 208085) is an autosomal recessive multisystem disorder that may be associated with germline VPS33B mutations. VPS33B is involved in regulation of vesicular membrane fusion by interacting with SNARE proteins, and evidence of abnormal polarised membrane protein trafficking has been reported in ARC patients. We characterised clinical and molecular features of ARC syndrome in order to identify potential genotype-phenotype correlations. The clinical phenotype of 62 ARC syndrome patients was analysed. In addition to classical features described previously, all patients had severe failure to thrive, which was not adequately explained by the degree of liver disease and 10% had structural cardiac defects. Almost half of the patients who underwent diagnostic organ biopsy (7/16) developed life-threatening haemorrhage. We found that most patients (9/11) who suffered severe haemorrhage (7 post biopsy and 4 spontaneous) had normal platelet count and morphology. Germline VPS33B mutations were detected in 28/35 families (48/62 individuals) with ARC syndrome. Several mutations were restricted to specific ethnic groups. Thus p.Arg438X mutation was common in the UK Pakistani families and haplotyping was consistent with a founder mutation with the most recent common ancestor 900–1,000 years ago. Heterozygosity was found in the VPS33B locus in some cases of ARC providing the first evidence of a possible second ARC syndrome gene. In conclusion we state that molecular diagnosis is possible for most children in whom ARC syndrome is suspected and VPS33B mutation analysis should replace organ biopsy as a first line diagnostic test for ARC syndrome.     

Clinical, biochemical and molecular genetic features of Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) has traditionally been considered a disease causing severe and permanent visual loss in young adult males. In nearly all families with LHON it is associated with one of three pathogenic mitochondrial DNA (mtDNA) mutations, at bp 11778, 3460 or 14484. The availability of mtDNA confirmation of a diagnosis of LHON has demonstrated that LHON occurs with a wider range of age at onset and more commonly in females than previously recognised. In addition, analysis of patients grouped according to mtDNA mutation has demonstrated differences both in the clinical features of visual failure and in recurrence risks to relatives associated with each of the pathogenic mtDNA mutations. Whilst pathogenic mtDNA mutations are required for the development of LHON, other factors must be reponsible for the variable penetrance and male predominance of this condition. Available data on a number of hypotheses including the role of an additional X-linked visual loss susceptibility locus, impaired mitochondrial respiratory chain activity, mtDNA heteroplasmy, environmental factors and autoimmunity are discussed. Subacute visual failure is seen in association with all three pathogenic LHON mutations. However, the clinical and experimental data reviewed suggest differences in the phenotype associated with each of the three mutations which may reflect variation in the disease mechanisms resulting in this common end-point.     

Male pseudohermaphroditism: Genetics and Clinical delineation

Summary The genetics and clinical delineation of male pseudohermaphroditism are reviewed. These disorders are categorized initially by their genetic etiology-cytogenetic, Mendelian, or teratogenic. It is especially important to distinguish cytogenetic forms, usually associated with 45,X/46,XY mosaicism, from Mendelian (genetic) forms because in the former the prevalence of gonadoblastomas or dysgerminomas is about 15–20%. Genetic forms include (1) those associated with a multiple malformation pattern, (2) those due to an error in adrenal or testicular hormonal biosynthesis, (3) complete testicular feminization, (4) incomplete testicular feminization, (5) Reifenstein syndrome, (6) pseudovaginal perineoscrotal hypospadias, and (7) agondia, and possibly other conditions. Incomplete testicular feminization and the Reifenstein syndrome may or may not represent varied expressivity of the same trait. The designation pseudovaginal perineoscrotal hypospadias is appropriate only if specific constellations of clinical features are present and if no metabolic abnormalities are demonstrable. Etiology and available genetic data are reviewed for each of these disorders.     

Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma

The effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared with that of tumors containing BRAF(V600E) mutations and tumors wild type for both (WT). Clinical outcome data were obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAF(V600E) were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. Seventy-five percentage of NRAS mutations occurred in tumors >1 mm thick (BRAF(V600E) 40%, WT 34%); 75% of NRAS mutations had >1 mitosis/mm(2) (BRAF(V600E) 40%, WT 55%). When compared to WT, multivariate analysis of melanoma-specific survival (MSS) identified NRAS mutations as an adverse prognostic factor [hazard ratio (HR) 2.96; P = 0.04] but not BRAF(V600E) mutations (HR 1.73; P = 0.23). NRAS mutations were associated with thicker tumors and higher rates of mitosis when compared to BRAF(V600E) and WT melanoma and independently of this, with shorter MSS.     

Clinical and genetic features of familial pituitary adenomas.

Inherited or familial pituitary tumor syndromes such as multiple endocrine neoplasia type 1 and Carney complex provide an important insight into the genetics and molecular pathology of endocrine cancers. Our understanding of these conditions is expanding rapidly due to the identification of the genes and proteins affected and the availability of murine knockout models. The successes achieved to date in understanding multiple endocrine neoplasia type 1 and Carney complex have helped in the identification and study of new inherited pituitary tumor syndromes such as isolated familial somatotropinomas. This review assesses the current status of research into the clinical features, genetics and molecular pathologies of multiple endocrine neoplasia type 1, Carney complex, and isolated familial somatotropinomas, and details ongoing work to delineate familial isolated pituitary adenomas, a potentially new clinical entity.