BRCA 1/BRCA 2 Pathogenic/Likely Pathogenic Variant Patients with Breast, Ovarian, and Other Cancers.

The demographic and clinical characteristics of patients who have BRCA 1/BRCA 2 pathogenic/likely pathogenic variants may differ from their relatives who had BRCA-related cancer. In this study, we aimed to demonstrate the clinical and demographic findings of patients who had BRCA-related cancer and to assess the differences comparing their relatives who had BRCA-related cancer with breast, genital tract, prostate, and pancreas cancers as well. The results of sequencing analysis of 200 cancer patients (190 women, 10 men) who have been directed to genetic counseling with an indication of BRCA1/BRCA2 testing from different regions across 9 medical oncology centers were retrospectively analyzed. A total of 200 consecutive cancer patients who harbored the BRCA1/BRCA2 pathogenic/likely pathogenic variant (130 (65%) patients harbored BRCA 1 pathogenic/likely pathogenic variant, and 70 harbored BRCA 2 pathogenic/likely pathogenic variant) were included. Of these, 64.0% had breast cancer (43.8% of them had the triple-negative disease, and about 2.3% had only the HER-2 mutant), 31.5% had genital cancers (92.1% of them had ovarian cancer, 3.2% had endometrium, and 1.6% had peritoneum cancer as the primary site and mostly serous adenocarcinoma was the most common histopathology and 14.3% of the patients had endometrioid adenocarcinoma), 3.5% had prostate (median time from metastasis to castration-resistant status was 28 months) and 1.0% had pancreas cancer. Newly diagnosed cancer (breast and ovary) patients who had BRCA 1/BRCA 2 pathogenic/ likely pathogenic variant were younger than their previous cancer diagnosed (breast, ovary, and pancreas) parents who harbored BRCA pathogenic/likely pathogenic variant. We suggest that the genetic screening of BRCA 1/ BRCA 2 pathogenic/likely pathogenic variant is needed as a routine screening for those with a personal or family history of breast, ovarian, tubal, or peritoneal cancer. In addition, once BRCA 1 or BRCA 2 germline pathogenic variant has been identified in a family, testing of at-risk next-generation relatives earlier can identify those family members who also have the familial pathogenic variant, and thus need increased surveillance.

The frequency of celiac disease in children with autoimmune thyroiditis.

BACKGROUND AND AIMS: Although the presence of autoimmune thyroiditis (AT) in celiac disease (CD) has been well documented among adults, CD in AT has been less reported in children. We aimed to investigate the frequency of CD in children with AT. Materials and Methods : This prospective study was carried out from October 2015 to August 2016 and included 66 patients with AT. Firstly, total IgA and tissue transglutaminase antibody (tTG) IgA levels were measured. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastroduodenoscopy for a definitive diagnosis of CD. RESULTS: Sixty-six patients with AT (52 female) with mean age of 14.68 ± 3.18 years were enrolled. IgA deficiency was found in four patients. Only three of 66 patients (4.5%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA, and only one of them (1.5%) had positive EMA antibodies. Gastroduodenoscopy was performed in this patient. The result of pathological investigation was compatible with CD. Furthermore, one patient with AT had been diagnosed with CD previously. CONCLUSIONS: Two (3.0%) of 66 patients with AT were found to have CD. According to the results, we assume that there is a close relationship between CD and AT disease. However, there is a need for multicentric, prospective studies that would support our findings.

A randomised controlled study comparing valethamate bromide and placebo in shortening the duration of active labour.

The aim of this study is to compare the efficacy and safety of valethamate bromide and placebo against placebo in shortening the duration of active labour. A prospective randomised trial of 158 low-risk women in spontaneous labour was conducted. After evaluation of the patients according to exclusion criteria 30 women were given valethamate bromide (Group 1) and 32 women were given placebo (Group 2). Labour duration was the main outcome measure. The duration of the active phase after starting the treatment was similar in the two groups at 225 and 219 min, respectively. However, differences were not significant between the 2 groups. Side effects such as tachycardia, flushing of the face and dryness of mouth were noted with valethamate bromide administration. In conclusion, valethamate bromide did not significantly shortened the duration of active labour in nulliparous women with a singleton pregnancy at term.

Is the Left Kidney the Right One for Kidney Donation in Women Planning on Future Pregnancy?

The kidney transplantation surgery requires left nephrectomy because of the anatomical disadvantages. But hydroureteronephrosis is the most significant renal functional alteration of pregnancy, accounted for by both hormonal and mechanical factors. Dilatation of the ureters and renal pelvis is more prominent on the right side than the left side and is seen in up to 80% of pregnant women. A 23-year-old woman who become pregnant after 4 months from left kidney donation was admitted to our emergency department with acute right kidney injury during her 39(th) week of pregnancy. She did not response to conservative treatment and required emergency delivery because of the progressive increase in her serum creatinine levels. After delivery, progressive decrease at creatinine level had been observed and in one month, it had reached the normal level. Mother candidates should be advised they donate their kidneys after completing their childbearing if possible, or undergo right nephrectomy.

A randomised controlled study comparing valethamate bromide and placebo in shortening the duration of active labour.

The aim of this study is to compare the efficacy and safety of valethamate bromide and placebo against placebo in shortening the duration of active labour. A prospective randomised trial of 158 low-risk women in spontaneous labour was conducted. After evaluation of the patients according to exclusion criteria 30 women were given valethamate bromide (Group 1) and 32 women were given placebo (Group 2). Labour duration was the main outcome measure. The duration of the active phase after starting the treatment was similar in the two groups at 225 and 219 min, respectively. However, differences were not significant between the 2 groups. Side effects such as tachycardia, flushing of the face and dryness of mouth were noted with valethamate bromide administration. In conclusion, valethamate bromide did not significantly shortened the duration of active labour in nulliparous women with a singleton pregnancy at term.

Late effects of childhood ALL treatment on body mass index and serum leptin levels.

BACKGROUND: It is well known that survivors of acute lymphoblastic leukemia (ALL) show a tendency to become overweight. Cranial irradiation (CRT), is considered to be the primary risk factor for development of obesity. AIMS: The aim of our study was to evaluate body mass index (BMI) and serum leptin levels in survivors of childhood ALL. METHODS: Subjects (Group I) consisted of 93 survivors of childhood ALL (53 males > or = 9 years old, 40 females > or = 8 years old) diagnosed between January 1975 and December 2002 in the Hematology-Oncology Division in Cerrahpasa Medical Faculty, Istanbul University after a follow up 10.21 +/- 4.90 (mean +/- SD) years. Fifty healthy individuals of similar chronological age were taken as controls (29 males, 21 females). Seventy-four subjects had received radiotherapy (Group IA) and 19 had not (Group I B). RESULTS: In Group I, BMI was significantly higher than in Group II (21.65 +/- 4.02 vs 20.31 +/- 3.49, p = 0.04). However, BMI was significantly higher only in Group I A (21.83 +/- 4.27) than in Group II (p = 0.032). Leptin levels were significantly higher in Group I A females than in Group II females. There was a significant correlation between BMI-SDS and serum leptin levels in group IA females. CONCLUSIONS: Leukemia treatment leads to obesity. Higher leptin levels in girls may suggest that sex may be a differentiating factor for this late effect.

Response to growth hormone with respect to pubertal status on increased dose in idiopathic growth hormone deficiency: an analysis of Turkish children in the KIGS database (Pfizer International Growth Study).

AIM: To compare the growth response to growth hormone (GH) treatment in patients with idiopathic GH deficiency (IGHD) who were prepubertal with the response of those who were pubertal at the onset of GH therapy on an increased GH dose. PATIENTS AND METHODS: Among the Turkish patients enrolled in the Pfizer International Growth Study (KIGS) database with the diagnosis of IGHD, the growth data over 2 years of GH therapy were analyzed longitudinally of 113 (79 M) prepubertal (Group 1) and 44 (33 M) pubertal (Group 2) patients. Pubertal signs were reported to be present initially or to have appeared within 6 months of GH therapy in Group 2. Mean +/- SD age at onset of therapy was 8.7 +/- 3.5 and 13.5 +/- 1.8 years; height SDS -4.2 +/- 1.4 and -3.2 +/- 1.1 (p < 0.05) in Groups 1 and 2, respectively. Mid-parental height (MPH) SDS did not show a significant difference between the two groups (-1.5 +/- 1.1 vs -1.7 +/- 1.1). RESULTS: Delta height SDS over 2 years of therapy was significantly higher in Group 1 (1.1 +/- 1.0) than in Group 2 (0.7 +/- 0.6) (p <0.05) in spite of a significantly lower dose of GH (14.6 +/- 3.3 in Group 1 vs 17.0 +/- 3.1 IU/m2/week in Group 2, p < 0.05). Ht--MPH SDS showed an increase from -2.4 +/- 1.7 to -1.4 +/- 1.5 in Group 1 and from -1.5 +/- 1.5 to -0.8 +/- 1.3 in Group 2. Overall delta height SDS showed negative correlations with age (r = -0.32), height SDS (r = -0.41) and height--MPH SDS (r = -0.40) at onset of therapy (p < 0.001). CONCLUSIONS: These data show that in IGHD the slight increase (15-20%) in the dose of GH during puberty was not adequate to maintain height velocity at the same magnitude as in prepuberty, and thus was not cost effective.

Feminizing surgical management of intersex patients.

The study's objective was to evaluate the results of surgical modalities for children with ambiguous genitalia. The records of 55 patients who were reared as females between 1985 and 2001 were reviewed regarding diagnosis, age at surgery, operative procedures, and outcome. The mean age at surgery was 3.5 years, and the follow-up period averaged 4.1 years with a range of 2 months-17 years. The types of reconstructive surgical techniques were clitorovaginoplasty in 29, staging clitoral surgery and vaginoplasty in seven, clitoroplasty in five, total urogenital mobilization (TUM) in three, vaginal bowel substitution in two, clitoridectomy in one, and gonadectomy in six, and two are waiting for vaginal substitution surgery after gonadectomy. The main complications were vaginal stenosis in four patients. All of the TUM patients had good appearances of their urethral orifice and vagina, all of them were continent, and none of them had urinary tract infections. With our limited experience with the TUM procedure, we feel that it is possible to obtain a better cosmetic and functional result with an easier technique. Among the 10 patients of postpubertal age, none of them had had sexual experience. Eight of the postpubertal patients asked questions about their reproductive status. Patients with an intersex disorder should be informed about their problems, especially about their reproductivity.

Growth and IGF-1 levels of children with familial Mediterranean fever on colchicine treatment.

OBJECTIVE: To evaluate growth process and insulin like growth factor-1 (IGF-1) levels in children with familial Mediterranean fever (FMF). METHODS: This prospective study group consisted of 51 children with FMF under colchicine therapy (20 boys, 31 girls) and 42 healthy children (22 boys, 20 girls). All children were prepubertal. Bone ages and IGF-1 levels were determined in all cases. Height velocity (HV), height standard deviation score (SDS), target height and target height SDS were calculated. RESULTS: There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and diseased subjects. HV of children with FMF did not differ significantly from the control group. There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and FMF subjects. HV of children with FMF did not differ significantly from the control group. There was no significant correlation between disease duration, number of attacks, erythrocyte sedimentation rate and HV, HSDS and IGF-1 levels of FMF patients. There was positive correlation between cumulative colchicine dose and HV (r = 0.29). CONCLUSION: Growth and IGF-1 levels of children with FMF do not differ from their healthy peers. However, there was positive correlation between HV and cumulative colchicine dose. This study suggests that colchicine not only has no adverse influence on growth, but more by suppressing disease activity and inflammation it has an enhancing role.

Effect of treatment on growth in congenital adrenal hyperplasia.

In 22 patients with congenital adrenal hyperplasia (CAH), the effect of treatment on growth was evaluated retrospectively. The degree of control with treatment had generally been assessed by measurements of serum 17-hydroxyprogesterone (17-OHP) and/or urinary pregnanetriol levels. In 20 patients, there were no significant differences in both height SDS for bone age (-2.05 +/- 1.89 vs -1.85 +/- 1.30) and height SDS for chronological age (CA) (0.23 +/- 1.94 vs -0.36 +/- 1.81) in a mean uninterrupted treatment period of 5.80 +/- 3.58 years. Further analysis in salt-losers and nonsalt-losers separately showed that height SDS for bone age had decreased in the salt-losers and had increased in the nonsalt-losers. Six patients had signs of early puberty. In 22 patients, there was a negative correlation between the prednisolone dose on one hand and height velocity SDS for CA and bone age velocity on the other. It was also found that the mean serum levels of 17-OHP did not always reflect the degree of long term control measured by auxological parameters. These findings indicate that our treatment in the patients did not result in a significant improvement in height prognosis. We can conclude that growth prognosis in CAH patients can be improved by relying on auxological parameters rather than serum 17-OHP and urinary pregnanetriol levels for monitoring control. Special attention should be paid to salt-losers in this respect.

Evaluation of growth hormone secretion and insulin-like growth factor-1 in prepubertal children with thalassemia.

Growth retardation is a clinical feature of patients with thalassemia major, and endocrine studies have frequently revealed the presence of normal growth hormone (GH) secretion. The present study was undertaken in 14 prepubertal thalassemic children (9 males and 5 females), aged 2(2/12) to 10(3/12) years, with the aim of evaluating GH response to i.v. arginine, oral L-dopa stimulation and insulin-like growth factor-1 (IGF-1) levels. Eleven patients had peak serum GH levels less than 7 ng/ml and two patients had peak serum GH levels of 7-10 ng/ml with arginine. Similarly, 10 patients had peak levels less than 7 ng/ml and one patient had a peak level of 7-10 ng/ml with L-dopa. Thus, nine of the patients had GH deficiency and two had partial GH deficiency. Three patients had elevated basal GH values. The serum IGF-1 levels in the patients were not statistically different from the levels in the controls, but three patients had low IGF-1 values. These findings suggest a defect in the regulatory mechanisms of GH secretion.

Intestinal effects of iron deficiency anemia in children.

A group of 11 children with iron deficiency anemia were studied with respect to intestinal structure and function. In six cases there were histological abnormalities of intestinal mucosa in varying degrees consisting of villous damage, increased activity in the crypts, increased lymphoplasmocytic infiltration and changes in the surface epithelium. Ultrastructurally, microvilli lesions, mitochondrial changes and an increase in lysosomes were observed. Relative malabsorption of iron and d-xylose malabsorption were present in a minority of patients. Functional and structural changes were correlated. Our results suggest that these changes are due to impairment of cell metabolism.