Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.     

Immunohistochemical localisation of 3β-hydroxysteroid dehydrogenase in<Emphasis Type="Italic"> Sarcocystis</Emphasis> spp.

3-Hydroxysteroid-dehydrogenase (3-HSD) is an isoenzyme that catalyses an essential step in the synthesis of all classes of active steroid hormones. The presence of steroid hormones of the vertebrate type in invertebrates is acknowledged in addition to a group of steroid-like hormones called ecdysteroids that were present in arthropods and helminths. In the present study, 3-HSD was detected in the bradyzoites enclosed in sarcocysts of Sarcocystis spp. with immunohistochemistry. The results suggest that self-originating steroid hormones may play important roles in the development of Sarcocystis spp., and possibly in the regulation of the reciprocal immune interaction between the host and these parasites.     

Spindle cell lipoma in an intramuscular lipoma

Intramuscular lipoma (IML) is a relatively common variant of lipomas. The most important sites for IML are the large muscles of the extremities. Spindle cell lipoma (SCL) is a rare and distinct variant of lipoma. Most SCL arise in the neck, shoulders or back. It has also been described in unusual sites, such as the oral cavity, larynx, bronchus, breast, orbit and extremities. However, localization of a SCL in an IML has not been described yet. Thus, we present the first SCL located in an IML, which was localized underneath the fascia and embedded within the left sartorius muscle of a 55-year-old man. Microscopically, the SCL component of the tumor was sharply circumscribed by a fibrous capsule and clearly separated from the IML in which it was localized. The collagen-forming spindle cells of the SCL showed neither atypia nor pleomorphism. These cells stained positive for CD34, while the mature fat tissue component of the SCL was positive for S-100 protein and negative for CD34. Spindle cells were negative for S-100 protein. Vimentin stained both components of the SCL, as well as the striated muscle fibers and mature fat tissue of the IML. In conclusion, careful morphological observation along with immunohistochemistry for CD34 and S-100 protein are essential to differentiate this rare tumor from lesions that enter the differential diagnosis.     

β-Globin chain abnormalities with coexisting α-thalassemia mutations

Introduction

The frequency of hemoglobinopathies is still high in Adana, the biggest city of the Cukurova Region that is located in the southern part of Turkey. Our aim was to identify the concomitant mutations in α- and β-globin genes which lead to complex hemoglobinopathies and to establish an appropriate plan of action for each subject, particularly when prenatal diagnosis is necessary.

Material and methods

We studied the association between the β-globin gene and α-thalassemia genotypes. The reverse hybridization technique was employed to perform molecular analysis, and the results were confirmed by amplification refractory mutation system (ARMS) or restriction fragment length polymorphism (RFLP) technique.

Results

We evaluated 36 adult subjects (28 female and 8 male; age range: 18-52 years) with concomitant mutations in their α- and β-globin genes. The –α^3.7/αα deletion was the commonest defect in the α-chain as expected, followed by α^3.7/–α^3.7 deletion. Twenty-five of 36 cases were sickle cell trait with coexisting α-thalassemia, while seven Hb S/S patients had concurrent mutations in their α-genes. The coexistence of α^PolyA-2α/αα with Hb A/D and with Hb S/D, which is very uncommon, was also detected. There was a subject with compound heterozygosity for β-globin chain (–α^3.7/αα with IVSI.110/S), and also a case who had –α^3.7/αα deletion with IVSI.110/A.

Conclusions

Although limited, our data suggest that it would be valuable to study coexisting α-globin mutations in subjects with sickle cell disease or β-thalassemia trait during the screening programs for premarital couples, especially in populations with a high frequency of hemoglobinopathies.     

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background

Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods

Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results

3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions

The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

     

Effects of alendronate and hormone replacement therapy, alone or in combination, on bone mass in postmenopausal women with osteoporosis: a prospective, randomized study

The effectiveness of hormone replacement therapy (HRT) and alendronate, alone and in combination, was evaluated in 120 postmenopausal patients with osteoporosis with bone mineral density (BMD) measurements at least 2 SD below the mean value for young premenopausal subjects. They had no contra-indications to HRT or alendronate use and were randomized to three different treatment groups. Group I was treated with micronized 17 beta-oestradiol 2 mg and norethisterone acetate 1 mg/day per os, group II received alendronate 10 mg/day per os and group III received micronized 17 beta-oestradiol 2 mg, norethisterone acetate 1 mg/day per os and alendronate 10 mg/day per os for 1 year. Elementary calcium 1500 mg/day was supplied to patients in all three groups. Spinal and femoral neck BMD and markers of bone mineral metabolism were measured on each patient before treatment and 6 and 12 months after treatment in 95 patients. At the end of the 12th month, significant increases in spinal and femoral neck BMD were found in all groups. Increases in spinal BMD were significantly higher in patients treated with alendronate and alendronate with HRT when compared with patients treated with HRT only. No significant difference was found in femoral neck BMD changes between the groups. Significant decreases in bone resorption and markers of bone formation were observed in all groups. Alendronate was found to be more effective than HRT and could have a very beneficial effect when added to the HRT regimen in patients with postmenopausal osteoporosis. Alendronate might also be used in postmenopausal patients with osteoporosis when HRT is contra-indicated or when there is reluctance to use hormonal treatment.     

Cell cycle markers have different expression and localization patterns in neuron-like PC12 cells and primary hippocampal neurons

Recent studies have indicated that bone marrow stromal cells (BMSCs) have significant tropism towards glioma which makes them play an important role in carrying genes/drugs to inhibit the growth of glioma as cell vehicles. But BMSCs may differentiate into neural cells under entocranial environment and few researches support the idea that neurally differentiated bone marrow stromal cells (N-D-BMSCs) still hold the capacity of migrating to the tumor sites. The aim of our study was to investigate the tropism of N-D-BMSCs towards C6 glioma. In vitro migration assay was employed by transwell co-culture system and Student's t-test analysis indicated that N-D-BMSCs had the significant tropism towards C6 glioma-conditioned medium (GCM) (P < 0.01). Furthermore, the vascular endothelial growth factor (VEGF) bioactivity of the C6 GCM was neutralized by the anti-rat VEGF antibody and our data suggested that the VEGF from C6 GCM hold chemoattraction for N-D-BMSCs and some other cytokines from the C6 GCM may be responsible for the chemoattraction for N-D-BMSCs. In vivo migration assay was carried out with cells transplantation and one way ANOVA analysis indicated that the tropism of N-D-BMSCs towards C6 glioma sites presented time variation (P-value = 2.9E−20). Moreover, multiple comparisons for the time variables with the Student's t-test and the results suggested that the migration capacity of N-D-BMSCs towards C6 glioma sites reach the peak on the 7th day after transplantation. These results demonstrate that N-D-BMSCs as well as BMSCs have significant tropism towards C6 glioma.     

Bacteremia in childhood cancer

Infection-related mortality affects the overall survival rates of children who are receiving treatment for cancer. The leading cause of mortality is bacteremia and sepsis related to it in febrile neutropenic patients. All positive blood cultures of febrile neutropenic patients treated in the Department of Pediatric Hematology-Oncology, Cerrahpasa Medical School, between January 1995 and January 2001 were reviewed. Cultures grew 159 micro-organisms, 95 (60 per cent) of which were Gram-positive bacteria, 56 (35 per cent) were Gram-negative bacteria and eight (5 per cent) were fungi. Coagulase-negative staphylococci (63, 40 per cent) and S. aureus (8, 5 per cent) were the most frequent Gram-positive pathogens. Klebsiella, E. coli, Enterobacter and Pseudomonas infections were the primary Gram-negative pathogens. Twenty cases were lost because of sepsis: in 11 cases (55 per cent) Gram-negative bacteria, in eight cases (40 per cent) Gram-positive bacteria, and in only one case a fungus were the causative organisms. Although vancomycin was not included in the first-line treatment, the mortality rate of Gram-positive bacteremia was 8 per cent. In Gram-negative bacteremia it was 20 per cent. Gram-negative pathogens, which were resistant to multiple antibiotics, caused the mortality. Drug resistance and mortality due to micro-organisms must be taken into consideration while febrile neutropenia protocols are prepared.     

The effect of tibolone on endometrial IGF-1 and IGFBP-1 levels in ovariectomized rats

OBJECTIVE: The goal of this study was to search the effects of two different doses of tibolone on endometrial IGF-1 and IGFBP-1 levels in ovariectomized rats. METHODS: Eighteen adult, female, 80-90-days-old, Wistar rats with an average weight of 250 g underwent bilateral ovariectomy under general anesthesia. After waiting for 4 weeks, they were randomized into three groups to receive either oral tibolone in two different doses or placebo. The treatment was continued for 5 weeks, and then the rats were sacrificed and the endometria were analyzed. RESULTS: Low columnar epithelium of the endometrial surface, longer epithelium and stratified squamous epithelium were seen in the control, low-dose and high-dose groups, respectively. The staining intensity of IGF-1 was mild in control, and moderate in both treatment groups, the difference between control the treatment groups was significant (P=0.015 for group L, and P=0.03 for group H). The staining intensity of IGFBP-1 was moderate in control, and strong in groups L and H. Again the difference was significant between control and both treatment groups (P=0.039 for grup L, and P=0.03 for group H). No significant difference was noted between each treatment group for both IGF-1 and IGFBP-1. CONCLUSION: Tibolone caused histological changes in endometrium and stimulated IGF-1 and IGFBP-1 staining. Both low and high dose treatments led to moderate and strong staining intensities for IGF-1 and IGFBP-1, respectively. The strong staining intensity of IGFBP-1 is likely due to the progestagenic effect of tibolone.     

Molecular Characterization of a Full Genome Turkish Hepatitis C Virus 1b Isolate (HCV-TR1): A Predominant Viral Form in Turkey

Based on direct sequencing information from 5UTR and NS5B regions, we identified subtype 1b as a predominant hepatitis C virus genome in Turkey, which affected more than 91% of 79 patients studied. Next, the full genome sequence of a Turkish 1b isolate was obtained by the cloning of polypeptide-encoding region into 7 overlapping fragments. Turkish 1b isolate, which was named HCV-TR1, comprises 9361 nucleotides, including 306 nucleotides of 5UTR, a single long open reading frame of 9033 nucleotides, and 22 nucleotides of 3UTR. When compared to HCV 1b polypeptide sequences available at GenBank, the predicted polypeptide displayed a total of 36 amino acid substitutions, of which 16 was specific for HCV-TR1 isolate. Despite these changes, major structural and functional motifs of HCV proteins were maintained in HCV-TR1. In contrast, HCV-TR1 displayed amino acid substitutions in 6 out of 9 major cytotoxic T-cell epitopes. These data suggest that HCV-TR1 encodes functionally intact viral proteins, but it also encodes altered viral epitopes, which may affect host immune-response.