Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas.

Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

Outcome of pregnancies in a large cohort of women with acromegaly.

OBJECTIVE: To assess the outcome of pregnancies in a large cohort of women with acromegaly. DESIGN AND METHODS: This is a retrospective analysis of 31 pregnancies in 20 patients with acromegaly. RESULTS: Twenty-seven pregnancies resulted in healthy offspring, and 4 resulted in abortion. Three patients underwent transsphenoidal surgery during pregnancy. IGF-1 levels remained elevated during pregnancy in 4 pregnancies and normalized in 23 cases. Fifteen cases were followed during pregnancy without any medical or surgical treatment, and 13 of these exhibited normal IGF-1 levels. Before or during pregnancy, somatostatin receptor ligands usage was not associated with higher risk for adverse outcomes. Arterial hypertension worsening (45%) and impairment of glucose levels (32%) were the most common complications during pregnancies. There were no maternal or neonatal deaths. One woman delivered twins. Two cases of congenital malformations and one with foetal macrosomia were observed. Caesarean delivery was performed in sixteen cases. CONCLUSION: Our study confirms the impact of gestation on IGF-1 levels. However, it also indicates that acromegaly still holds an increased risk for worsening of comorbidities, especially in uncontrolled patients.

Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas

Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

Role of injection pressure, flow and sclerosant viscosity in causing cutaneous ulceration during sclerotherapy.

The objective of the study is to evaluate the viscosity of popular sclerosants and their flow hydrodynamics through a syringe/needle to further discuss Miyake's old, venous-capillary reflux theory, using additional objective data. The following sclerosing agents were tested in the study: 75% dextrose (D75%); 50% dextrose (D50%); 5% ethanolamine oleate (Etha5%); 0.5% laureth-9 (Aet0.5%) and 0.1% sodium tetradecyl sulphate (STS0.1%). Using 5 mL syringes and 27G needles, the resulting pressures and flows for each sclerosant agent were measured. To do this, a three-way stopcock was connected between the syringe and the needle so that an arm of the stopcock could be used to measure injection pressures with a digital monitor in 1 mmHg increments. Two trials were performed: in trial 1, the syringe was attached to a Samtronic 680 infusion pump and in trial 2, the solutions were injected manually. The observed sclerosant viscosities were as follows: D75%: 0.28 Poise; D50%: 0.12 Poise; Etha5%: 0.10 Poise; Aet0.5%: 0.07 Poise; and STS0.1%: 0.04 Poise. In trial 1 (constant flow), it was observed that D75%, which had the highest viscosity of the sclerosants tested, had the highest pressure readings. In trial 2 (constant pressure), the flow obtained with the D75% solution was lower than the flow of the other solutions. In conclusion, based on the rabbit study theory, vessel size and sclerosant viscosity and strength, not extravasation, play a role in causing ulceration from injection sclerotherapy. As a result, they all affect the potential of venous-capillary reflux being caused by sclerotherapy injection and, thus, the risk of postsclerotherapeutic cutaneous ulceration.

Occurrence Angiostrongylus vasorum (Baillet, 1866) (Nematoda, Angiostrongylidae) in Cerdocyon thous Linnaeus, 1766 (Carnivora, Canidae) in Minas Gerais State Brazil / Ocorrência de Angiostrongylus vasorum (Baillet, 1866) (Nematoda, Angiostrongylidae) em Cerdocyon thous (Linnaeus, 1766) (Carnivora, Canidae) no Estado de Minas Gerais

Registrou-se a ocorrência de A. vasorum em C. thous no Estado de Minas Gerais, e estudaram-se aspectos de sua ecologia nessa população de hospedeiros. A partir da necropsia de seis espécimes, observou-se a presença de A. vasorum nos pulmões e átrio direito de C. thous. No total foram coletados 24 espécimes de A. vasorum, com prevalência de 50 por cento, abundância média de 4±4,47, intensidade média de 8±3,00 e razão sexual (machos/fêmeas) de 1:1,19. As infrapopulações de A. vasorum apresentaram padrão de distribuição espacial agregado (ID=5,70 e K=0,355). Este é o primeiro registro de A. vasorum em C. thous no estado, descrito no município de Juiz de Fora(AU)

Occurrence Angiostrongylus vasorum (Baillet, 1866) (Nematoda, Angiostrongylidae) in Cerdocyon thous Linnaeus, 1766 (Carnivora, Canidae) in Minas Gerais State Brazil

Registrou-se a ocorrência de A. vasorum em C. thous no Estado de Minas Gerais, e estudaram-se aspectos de sua ecologia nessa população de hospedeiros. A partir da necropsia de seis espécimes, observou-se a presença de A. vasorum nos pulmões e átrio direito de C. thous. No total foram coletados 24 espécimes de A. vasorum, com prevalência de 50 por cento, abundância média de 4±4,47, intensidade média de 8±3,00 e razão sexual (machos/fêmeas) de 1:1,19. As infrapopulações de A. vasorum apresentaram padrão de distribuição espacial agregado (ID=5,70 e K=0,355). Este é o primeiro registro de A. vasorum em C. thous no estado, descrito no município de Juiz de Fora