Bisphosphonate treatment at spondylo-ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long-term follow-up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients with XYLT2-related pathogenesis.     

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.     

A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells

Here, we describe the characteristics of a Pt‐blue complex [Pt₄(2‐atp)₈(H₂O)(OH)] (2‐atp: 2‐aminothiophenol) as a prodrug for its DNA‐binding properties and its use in cancer therapy. The nature of the interaction between the Pt‐blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single‐ and double‐stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST‐1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro‐apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt‐blue complex under study grants premise for further studies.     

Cognition of the mothers of patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) has been found to be associated with cognitive impairment. However, few studies have addressed cognitive impairment among mothers of children with DMD. In the present study, the neuropsychological profiles of both carrier mothers (C-Ms) and noncarrier mothers (NC-Ms) were examined, and the findings were compared with healthy control mothers (HC-Ms). There were 90 participants, consisting of 31 C-Ms, 24 NC-Ms, and 35 HC-Ms, each of whom completed a neuropsychological test battery. C-Ms had poorer cognition performance in attention, working memory, immediate verbal memory, visuospatial skills, and executive functions than NC-Ms, and HC-Ms. This study provides evidence that there may be cognitive impairment in mothers of patients with DMD. The cognitive impairment of C-Ms has similarities to that seen in children with DMD.     

The results of cytogenetic analysis with regard to intracytoplasmic sperm injection in males, females and fetuses

OBJECTIVES: To determine the incidence of chromosome abnormalities among couples for whom intracytoplasmic sperm injection (ICSI) treatment was indicated and fetuses conceived through the ICSI procedure. METHODS: All cytogenetic results were evaluated retrospectively. Patients undergoing ICSI (n = 508) were classified according to the referring indications as: (1) males with severe infertility (87 azoospermia and 34 oligoasthenoteratozoospermia, OAT), (2) prior to ICSI (56 males and 61 females), and (3) following an unsuccessful ICSI procedure (132 males and 138 females). Fetuses conceived through ICSI (n = 475) were also classified into 4 groups according to the additional risk factors for chromosome abnormalities: ICSI (n = 185), ICSI + advanced maternal age (AMA, n = 215), ICSI + positive triple test result (TT, n = 50), and ICSI + abnormal ultrasound findings (USG, n = 25). RESULTS: An abnormal karyotype was found in 31.03% of males with azoospermia and 14.71% of males with OAT, in 3.57% of males and 1.64% of females in the group prior to ICSI, and in 5.30 and 5.07%, respectively, in the group following unsuccessful ICSI treatment. Gonosomal aneuploidies were predominant in males with azoospermia and autosomal rearrangements in males with OAT, while low-level sex chromosome mosaicism was found in females. The overall frequency of chromosome abnormalities in fetuses was 4.42% and varied in the different groups from 1.62% in ICSI, 2.79% in ICSI + AMA, 10.0% in ICSI + TT to 28.0% in ICSI + USG. The frequencies of the different types of chromosome abnormalities were as follows: balanced 1.05%, unbalanced 3.37%, familial 0.84%, de novo 3.37%, autosomal 3.58%, gonosomal 0.84%, numerical 1.89%, structural abnormalities 2.53%, and mosaicism 1.26%. CONCLUSION: Our results indicate that cytogenetic investigations of the ICSI parents and fetuses are essential for the families, genetic counselors and also reproductive centers. In fetal karyotyping, de novo structural chromosome abnormalities and mosaicism should be taken into consideration.     

Nitric oxide levels of aqueous humor after photorefractive keratectomy

PURPOSE: To measure the nitric oxide (NO) levels of aqueous humor in rabbits after photorefractive keratectomy (PRK) and to evaluate the alterations of NO levels according to the PRK surgery steps, ablation depth, and time. METHODS: Fifty eyes of 25 New Zealand white rabbits were included in the study. One eye was later randomly excluded from the study in order to equalize the number of eyes in groups. Eyes were divided into seven groups, each comprising seven eyes: unwounded control (Group 1), epithelial scrape (Group 2; aqueous humor samples taken at the 4th hour), superficial PRK (Group 3; samples taken at the 4th hour), deep PRK (Group 4; samples taken at the 4th hour), epithelial scrape (Group 5; samples taken at the 24th hour), superficial PRK (Group 6; samples taken at the 24th hour), and deep PRK (Group 7; samples taken at the 24th hour). The corneal epithelium was mechanically removed in surgical groups. The authors performed superficial corneal ablation (59 microm) in Groups 3 and 6 and deep corneal ablation (99 microm) in Groups 4 and 7. Aqueous humor samples were taken at the 4th hour (Groups 2-4) or 24th hour (Groups 5-7) after corneal surgeries. NO measurements were performed indirectly by using the Griess reaction with a spectrophotometer. RESULTS: Aqueous humor NO levels 4 hours after corneal surgery were statistically significantly lower than the control group (p<0.05). However, there was no difference among the surgical groups at the 4th hour (p>0.05). At the 24th hour, the deep PRK group had significantly lower NO levels than both the control group and Groups 5 and 6 (p<0.05). NO levels were normalized at the 24th hour in epithelial scrape and superficial PRK groups (p>0.05) but remained stable at lower levels in deep PRK groups (p<0.05). CONCLUSIONS: Corneal surgery caused low NO levels in aqueous humor 4 hours after surgery. However, 24 hours after surgery, NO levels normalized following epithelial scrape and superficial PRK and were stable at lower levels in the deep PRK group. Complications of deep PRK application are possibly induced by low NO existence in the aqueous humor.     

Depression and anxiety in hypothyroidism

The aim of the study was to determine the prevalence and severity of depression and anxiety in patients with hypothyroidism and to compare this with euthyroid patients. Thirty patients with hypothyroidism and 30 euthyroid controls attending the Endocrinology outpatient department of Celal Bayar University, Medical Faculty were included in the study. The hormonal screening was done by immunoassay and haemagglutination methods. Then, for psychiatric assessment, Hospital Anxiety and Depression Scale (HAD), Hamilton Depression Rating Scale (HAM-D), and Hamilton Anxiety Rating Scale (HAM-A) were used. There was no difference between the two groups in terms of demographic features. Total scores obtained from the scales used in the study did not differ significantly (p > 0.05). The frequency of items of both HAM-D and HAM-A did not show any differences in the two groups. By Wilks' Lambda discriminant analysis, depressive mood (HAM-D#1) was found to be the discriminating feature between the hypothyroid group and the euthyroid group. Therefore, depression and anxiety were not outstanding features in hypothyrodism. However, depression was more significant in the hypothyroid than euthyroid group.     

Differentiation of leukemic cells induced by short-course high-dose methylprednisolone in children with different subtypes of acute myeloblastic leukemia.

Differentiation of myeloid leukemic cells to mature granulocytes by high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) with a favorable antileukemic effect has previously been demonstrated in children with acute promyelocytic leukemia and acute myeloblastic leukemia (AML) M4. In the present study, three children with other morphological subtypes of AML (two AML M1, one AML M2) were given methylprednisolone (30 mg/kg/day) orally in a single dose. After a short-course (3 or 7 days) of HDMP treatment alone, a striking decrease in blast cells associated with an increase in maturing and abnormally nucleated polymorphonuclear-like cells some containing Auer rods were detected in all patients in peripheral blood or bone marrow smears. During HDMP treatment, in parallel to morphological improvements, marked increases in the percentage of cells expressing granulocytic antigen (CD15) were observed. The increase of CD15 expression on myeloid cells, together with the steady expression of CD34 and CD117 antigens in Casel(AML M1) , is suggestive of aberrant CD34 + CD117 + CD15 + cells, which may indicate the leukemic origin of the maturing myeloid cells. These results suggest that HDMP treatment may induce differentiation of myeloid leukemic cells in some children with different morphological subtypes of AML, and that the differentiation-inducing effect of HDMP should be explored in other malignant diseases.