Dynamics of hormonal disorders following unilateral orchiectomy for a testicular tumor

Testicular tumors and their treatment interfere with homeostasis, hormonal status included. The aim of the study was to evaluate hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors. One hundred twenty-eight men treated for a unilateral testicular tumor at our institution were included. The hormonal status was prospectively evaluated in 62 patients before orchiectomy, 120 patients 1 month after orchiectomy and 110 patients at least 1 year after the treatment. The concentrations of human chorionic gonadotropin (hCG), testosterone (T), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured. The clinically significant testosterone deficiency was defined either as testosterone <2.31 ng/mL or testosterone within the range of 2.31–3.46 ng/mL but simultaneous with T/LH ratio ≤1. Changes in hormone levels were significant: LH and FSH rose in the course of observation, and the concentration of hCG, testosterone, estradiol decreased. PRL concentration was the lowest at 1 month after orchiectomy. In multivariate analysis, the risk of the clinically significant testosterone deficiency was 0.2107 (95% CI 0.1206–0.3419) prior to orchiectomy, 0.3894 (95% CI 0.2983–0.4889) 1 month after surgery and 0.4972 (95% CI 0.3951–0.5995) 1 year after the treatment. The estradiol concentration was elevated in 40% of patients with recently diagnosed testicular cancer and that was correlated with a higher risk of testosterone deficiency after the treatment completion. Hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors are frequent. The malignant tissue triggers paraneoplastic disorders that additionally disturb the hormonal equilibrium

hCG-secreting malignancies – diagnostic pitfalls

We present a case of a 34-year-old male patient referred to our Uro-oncology Department with a suspicion of a metastatic germ cell tumour, owing to enlarged left testicle and elevated b-hCG concentration (39 mIU/mL). Impaired performance status caused by extensive pulmonary and liver metastases, accompanied by significant lymphadenopathy, necessitated prompt management. However, a testicular tumour was excluded on ultrasound imaging; a hydrocele only was found. The b-hCG concentration was not increasing (37 mIU/mL). We found a diagnosis of an extragonadal germ cell tumour doubtful, and a liver biopsy was performed. Due to the patient’s quick deterioration, we decided to commence pre-phase chemotherapy with cisplatin and etoposide, which resulted in a significant clinical improvement. The pathological examination, along with immunoassays, revealed undifferentiated cholangiocarcinoma, and the patient continued chemotherapy with a biliary tract cancer regimen, i.e. cisplatin and gemcitabine. Unfortunately, the clinical response was short-lived; the disease progressed, the patient was offered best supportive care and died two months after the diagnosis. The case underpins the literature review with respect to differential diagnosis of an elevated hCG concentration. In particular, we discuss ectopic secretion in non-trophoblastic and non-germinal malignancies and the causes of false positive assays.We present a case of a 34-year-old male patient referred to our Uro-oncology Department with a suspicion of a metastatic germ cell tumour, owing to enlarged left testicle and elevated β-hCG concentration (39 mIU/ml). Impaired performance status caused by extensive pulmonary and liver metastases, accompanied by significant lymphadenopathy, necessitated prompt management. However, a testicular tumour was excluded by ultrasound examination; a hydrocele only was found. The β-hCG concentration was not increasing (37 mIU/ml). We found a diagnosis  of an extragonadal germ cell tumour doubtful, and a liver biopsy was performed.  Due to the patient’s quick deterioration, we decided to commence pre-phase chemotherapy with cisplatin and etoposide, which resulted in a significant clinical improvement. The pathological examination, along with immunoassays, revealed undifferentiated cholangiocarcinoma, and the patient continued chemotherapy  with a biliary tract cancer regimen, i.e. cisplatin and gemcitabine. Unfortunately, the clinical response was short-lived; the disease progressed, the patient was offered best supportive care and died two months after the diagnosis. The case underpins the literature review with respect to differential diagnosis  of an elevated hCG concentration. In particular, we discuss ectopic secretion  in non-trophoblastic and non-germinal malignancies and the causes of false positive assays

Video-based Simulations: Considerations for Teaching Students with Developmental Disabilities

The use of video-based multimedia simulations for teaching functional skills to persons with developmental disabilities remains an unexplored application of technology for this group. This article examines the historical literature in this area, and discusses future considerations, design issues, and implications of using multimedia simulations. Implementation issues are presented, and suggestions regarding design, development, and application of multimedia simulations are offered. Considerations address the importance of appropriate role modeling and the combination of video-based simulation and in vivo training to foster generalization and maintenance in the context of transition to the real world.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

The Educational Case for a Simulated Lunar Base

An in depth study of interest in an addition to the science curriculum of the Worcester Public schools. The proposed addition is for a space science curriculum that can be combined with a simulated lunar exhibit

I.29 lymphoma cells express a nonmutated VH gene before and after H chain switch

The I.29 B cell lymphoma consists of IgM+ and IgA+ cells which express the same germ-line VH gene. IgA+ cells of the I.29 lymphoma were derived from the IgM+ cells by a typical H chain switch recombination event. The IgM+ cells can be induced with LPS to undergo H chain switching in culture. It has been proposed that the somatic hypermutation process is activated during H chain switch, since V genes expressed in IgG+ and IgA+ cells have more frequently undergone mutation than those expressed in IgM+ cells. We have investigated this question by sequencing VH genes expressed before and after H chain switch in the I.29 lymphoma. We have also sequenced the germ-line VH gene corresponding to the gene expressed by I.29 cells to determine whether the VH gene expressed in the IgM+ cells had already undergone somatic mutation. Our results indicate that somatic mutation was not activated in the precursor cell for the I.29 lymphoma, nor during isotype switch in I.29 cells. It is possible that cells of the I.29 lymphoma, or their precursor, have not received the signal which induces somatic mutation, or that I.29 cells belong to a subset of B cells that cannot be induced to undergo any (or much) somatic mutation