Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii.

Toxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl hydrazone (KG8) as the most promising compound; KG8 displayed potent in vitro activity against T. gondii but only marginal in vivo efficacy in a T. gondii animal model. To define the potential of this new lead compound, we now describe a baseline structure-activity relationship for this chemotype. Several derivatives displayed IC50's comparable to that of the control treatment pyrimethamine with little to no cytotoxicity. The best of these, KGW44 and KGW59, had higher metabolic stability than KG8. In an in vivo T. gondii murine model, KGW59 significantly increased survivorship. This work provides new insights for optimization of this novel chemotype.

Cytological features of melanoma in exfoliative fluid specimens.

AIMS: To describe the cytological appearances of melanoma in fluid specimens and potential diagnostic pitfalls in interpreting such specimens, which have been infrequently reported in the literature. METHODS: Cases of melanoma diagnosed at a single institution between 1993 and 2008 in cytology specimens of fluids (pleural, ascitic, cerebrospinal and other fluids), but excluding fine needle biopsy specimens, were identified and reviewed. RESULTS: 32 fluid specimens containing metastatic melanoma (from 26 patients) were identified. Most of the specimens were moderately cellular and showed moderate to marked nuclear pleomorphism. Mitotic figures and intranuclear cytoplasmic invaginations were identified in 11 (34.4%) and seven (21.9%) cases, respectively. Melanin pigment was seen in eight (25.0%) cases. Variable numbers of histiocytes were present, and mesothelial cells were present in body cavity fluid specimens. CONCLUSIONS: In fluid specimens, reactive mesothelial cells and histiocytes may mimic epithelioid melanoma cells. Awareness of the morphological features and diagnostic pitfalls of melanoma in fluids is necessary to avoid the potentially serious consequences of misdiagnosis.

Pallister-Hall syndrome: unreported skeletal features of a GLI3 mutation.

We describe two patients with Pallister-Hall syndrome (PHS), both with evidence of a generalized skeletal dysplasia as typified by upper and lower acromesomelic limb shortening and the previously unreported fibular hypoplasia, radio-ulnar bowing, and proximal epiphyseal hypoplasia. Genomic DNA was only available for sequencing analysis in patient 2 and the mutation, c.3386_3387delTT was detected in exon 14 of the GL13 gene. It is also possible that the findings in patient 1 represent the phenotypic expression of a novel GLI3 mutation. This report further expands the PHS phenotype and raises the possibility of specific GLI3 mutations resulting in more severe skeletal features. It also suggests that PHS should be included in the differential diagnosis of antenatally ascertained acromesomelic limb shortening and bowing with fibular hypoplasia particularly in the presence of polysyndactyly.

Phaeochromocytoma in two coatimundi (Nasua nasua).

Two unrelated coatimundi (Nasua nasua) had bilaterally enlarged adrenal glands at necropsy, and sections of the glands from both animals had histopathological features consistent with neoplasia. They were differentiated from an adrenal cortical tumour on the basis of their light microscopical morphology, immunoperoxidase staining and electron microscopic studies and a final diagnosis of phaeochromocytoma was made. To the authors' knowledge, these are the first reported cases of phaeochromocytoma in coatimundi.

Papillary ductal adenocarcinoma in the mammary glands of two horses.

Mammary gland neoplasms in horses are uncommon and may initially be confused with mastitis. Masses from the mammary glands of two horses with chronic discharges were examined by cytology and histopathology. Both masses were diagnosed as papillary ductal adenocarcinomas with extensive intraductal and intralobular involvement and only focal infiltration of the adjacent stroma. Complementary immunohistochemical studies were made of both fresh and formalin-fixed tumour tissue, and attempts were made to assess the steroid receptor status of fresh tissue biochemically to assess the possibility of hormonal treatment as an adjunct to surgery. The results of these tests for oestrogen and progesterone receptors were negative.

Disappearing lung echogenicity in fetal bronchopulmonary malformations: a reassuring sign?

Congenital bronchopulmonary malformations detectable on prenatal ultrasound include cystic adenomatoid malformation (CAM), lobar sequestration, and upper airway atresia. We describe three fetuses with prenatally detected intrathoracic lesions in which the associated pulmonary hyperechogenicity disappeared before delivery. In the first case of pulmonary sequestration, the infant was asymptomatic after birth. However, in a case of CAM and another with laryngeal atresia, respiratory distress developed after delivery, despite recent scans showing apparently normal lung fields. This experience suggests that ultrasonic resolution of hyperechogenic lung lesions in utero does not necessarily indicate resolution of the underlying pathology.