A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management

Abstract

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS.

Methods: Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed.

Results: During hormonal evaluation elevated serum concentration of FSH and LH and decreased serum concentration of estradiol were measured. The genetic testing revealed translocation 7;14 (t(7;14)) and inversion 7 in 22% of examined cells which confirmed the initial hypothesis of NBS. The diagnosis was finally verified by identifying a Slavic founder mutation, c.657_661del5, on both allels of the NBN gene. Furthermore, hormonal serum evaluation conducted after four weeks allowed the patient to be diagnosed with premature ovarian insufficiency (POI) suspected earlier on the grounds of preliminary examinations (ultrasound imaging and laboratory tests).

Conclusions: Chromosomal instability resulting from a mutation present in Nijmegen breakage syndrome patients might be a causative factor of premature ovarian insufficiency. Therefore, females diagnosed with NBS should undergo additional diagnostic procedures in order to determine further management and treatment.     

The height-, weight-, and BMI-for-age of Polish school-aged children and adolescents relative to international and local growth references

Background  

The growth of children is an indicator of health and society's wellbeing. Growth references are useful in monitoring a child's growth, which is a very important part of child care. Poland's growth references are not updated regularly. Although several growth reference ranges have been developed in Poland over recent years, sampling was restricted to urban populations of major cities. The aim of this study was to assess how well Polish children match with, or diverge from, regional charts and to compare them with international growth references.     

Matrix solid-phase dispersion (MSPD) in chromatographic analysis of essential oils in herbs

Matrix solid-phase dispersion (MSPD) is a simple and cheap sample preparation procedure allowing for the reduction of organic solvent consumption, exclusion of sample component degradation, improvement of extraction efficiency and selectivity, elimination of additional sample clean-up and pre-concentration step before chromatographic analysis.     

Inequalities in the psychological well-being of employed, single and partnered mothers: the role of psychosocial work quality and work-family conflict

Background  

A large body of international research reveals that single mothers experience poorer mental health than their partnered counterparts, with socioeconomic disadvantage identified as an important contributory factor in understanding this health disparity. Much less research, however, has focused specifically on the psychological well-being of single mothers who are employed, despite their growing presence in the labor force. Of the research which has considered employment, the focus has been on employment status per se rather than on other important work-related factors which may impact psychological health, such as psychosocial work quality and work-family conflict. The aim of this study was to: (1) compare employed single mothers and employed partnered mothers on measures of psychological distress, psychosocial work quality and work-family conflict; and (2) explore the potential role of work-family conflict and psychosocial work quality as explanations for any observed differences in psychological distress based on partner status.     

Is sonoelastography a helpful method for evaluation of parotid tumors?

Sonoelastography is a novel technique, useful in a noninvasive assessment of lesions in multiple organs. The aim of the study was to examine whether the combination of conventional ultrasonography (US) with sonoelastography might improve the reliability of parotid tumor evaluation. Fourty-three consecutive patients with parotid tumors were surgically treated at a single tertiary center at the Department of Otolaryngology, Head and Neck Surgery. The sample included 27 women and 16 men, aged 15–80 (the mean age = 54 years). The reference group constituted of 54 healthy volunteers. High resolution grayscale ultrasonography (US) was performed preoperatively using a 15 MHz linear array transducer. Elastograms (ES) were scored by the conventional Ueno 5-point scale from ES1 (blue-soft) to ES5 (the entire lesion and surrounding area shaded red-stiff). In addition, detailed stiffness values in kPa were collected. The group consisted of 33 patients with benign and 10 patients with malignant tumors. The mean stiffness value was 146.6 kPa in 10 malignant tumors (mostly ES4) and 88.7 kPa in 33 benign tumors (mostly ES2 and ES3). The differences in tissue stiffness between normal parotid parenchyma in the reference group and the mean value for all tumors in the examined group were statistically significant (p < 0.001), and so was the case with the differences between the benign and malignant tumors (p < 0.001). Low stiffness scores (ES1,2) were found in 2 malignant and 15 benign tumors while high scores (ES3,4) were found in 8 malignancies and 18 benign tumors. Sonoelastography overlapping elasticity to the grayscale images supports additional informations. Preferential selection of the lesions characterized by high stiffness (ES4) improves the differential diagnosis of parotid tumors but the large degree of uncertainty of this method should also be pointed out.     

Zonulin,inflammation and iron status in patients with early stages of chronic kidney disease

Background/aims

Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters.

Methods

Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays.

Results

Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin.

Conclusions

Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

     

Antineoplastic action of growth hormone-releasing hormone (GHRH) antagonists

Some of the antagonists of growth hormone-releasing hormone (GHRH) are able to inhibit the growth of various experimental human cancers. The antitumor effects of first antagonists seemed to be dependent mainly on the disruption of pituitary secretion of growth hormone (GH), followed by the reduction in the levels of circulating insulin-like growth factor (IGF)-1, an important growth factor for cancer cells. It seems obvious, that growth hormone deficiency (GHD) induced by GHRH antagonists with all its complications, could limit the beneficial effects of GHRH antagonists therapy, and decrease patients' quality of life. The discovery of local autocrine/paracrine production of GHRH and other related growth factors in many tumoral tissues, in combination with the wide expression of GHRH receptors on cancer cells, directed the research to the synthesis of more potent GHRH antagonists. These compounds exert strong inhibitory effects directly on tumor growth, with scarce endocrine action. The receptor-mediated mechanisms comprise complex and still not completely understood effects on intracellular signaling pathways that are strictly related to human tumorigenesis. This review summarizes recent patents and latest observations on the antineoplastic role of GHRH antagonists in human tumors with emphasis on potential therapeutic applications in clinical oncology.     

Modulation of ghrelin axis influences the growth of colonic and prostatic cancer cells in vitro

BackgroundThe risk of different cancers seems to be associated with obesity. Moreover, low ghrelin levels observed in obese people may be implicated in cancer development and progression. The aim of this study was to examine the direct effects of both forms of ghrelin (acylated and unacylated) and ghrelin receptor type 1a antagonist (D-Lys-GHRP-6) on the growth of murine colon cancer MC38 and human prostate cancer DU145 cell lines in vitro.MethodsThe cells were cultured for 72 h in the presence of rat or human acylated ghrelin (rG, hG), human unacylated ghrelin (hUAG), D-Lys-GHRP-6 (GHS-RA) applied either alone or jointly. The cell line growth was assessed by the colorimetric Mosmann method.ResultshUAG (10^?6, 10^?7 and 10^?10 M) inhibited MC38 cancer cell growth and, at some concentrations (10^?8, 10^?9, 10^?10 M), enhanced the antineoplastic effect of GHS-RA (10^?4 M). In turn, GHS-RA evoked a biphasic effect on MC38 cancer growth: inhibitory at 10^?4 M and stimulatory at 10^?5 and 10^?6 M. Moreover, GHS-RA at the highest examined concentration (10^?4 M) enhanced the cytostatic effect of FU. Human acylated and unacylated ghrelin and GHS-RA inhibited DU145 cancer growth with moderate and different potencies. A dose-response effect was observed for the inhibitory action of hG together with the synergistic effect of hUAG and GHS-RA.ConclusionThe obtained results indicate an involvement of the ghrelin axis in the growth regulation of colon and prostate cancers and may suggest new therapeutic options for these neoplasms.     

Peritoneal immune system in patients with advance epithelial ovarian cancer

The development of epithelial ovarian cancer is associated with changes in the peritoneal cavity microenvironment. Tumor cells produce different factors, which impairs differentiation, maturation, and function of antigen-presenting cells. In this review, we focus on selected cell populations in the peritoneal cavity immune system and their potential role in epithelial ovarian cancer immunopathogenesis. We devote most attention to dendritic cells because they are considered to be superior in their antigen-presenting ability, compared with both macrophages and B lymphocytes. We also present a brief characterization of tumor-infiltraiting cells in epithelial ovarian cancer patients.