Waning of Humoral Immunity to Vaccine-Preventable Diseases in Children Treated for Acute Lymphoblastic Leukemia: A Single-Center Retrospective Cross-Sectional Analysis.

Objective: The survival rates of children with acute lymphoblastic leukemia (ALL) have improved over the years, but infections remain a significant cause of morbidity and mortality. Chemotherapy has a range of harmful side effects including the loss of protective antibodies against vaccine-preventable diseases. The objective of this study was to evaluate the serological status of pediatric ALL cases before and after the intensive chemotherapy. Materials and Methods: Children treated and followed up for ALL at Dokuz Eylül University were included in this retrospective cross-sectional study. Antibody levels against hepatitis A, hepatitis B, and rubella were routinely assessed both at the time of diagnosis and six months after completion of chemotherapy. However, measles, mumps, and varicella antibody levels were evaluated just six months after the treatment. Results: Seventy-eight children who completed chemotherapy for ALL were recruited. All participants had nonprotective antibody levels for at least one of the diseases. The highest seropositivity rate was found for hepatitis A (55.1%) and the lowest for measles (17.9%) after chemotherapy. Overall, 50.7%, 30.6%, and 45.7% of the patients significantly lost their humoral immunity against hepatitis B, hepatitis A, and rubella, respectively. Patients in the higher-risk group for ALL had a lower seropositivity rate than the other risk group patients. There were statistically significant relations between the protective antibody rates of hepatitis A and varicella and the age of the patients. Except for the hepatitis A vaccination, pre-chemotherapy vaccination did not affect post-chemotherapy serology. On the other hand, all children with a history of varicella before the diagnosis showed immunity after chemotherapy. Conclusion: All patients, including those previously fully vaccinated, are at great risk of infection due to the decrease in protective antibody levels after chemotherapy. There is a need for routine post-chemotherapy serologic testing and re-vaccination based on the results obtained.

Salivary Sex Steroid Levels in Infants and the Relation with Infantile Colic

Objective: The hypothalamic-pituitary-gonadal axis is active during minipuberty, the timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been previously investigated. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female) while the remaining healthy infants constituted Group 2 (n=71, 47.9% female). Salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were measured by ELISA in duplicate. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar. However, in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs= 0.393, p=0.016 vs. Group 2, rs= 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs= 0.469, p=0.009 vs. Group 2, rs= -0.005, p=0.976). Conclusion: Random salivary sex steroid levels were similar in infants with and without infantile colic. However, in subjects with infantile colic, Esal levels in females were positively correlated with BMI and Tsal levels were higher later in the day among males. Thus, sex steroid production may be altered during minipuberty in subjects with infantile colic.

Quantification of overnight urinary gonadotropin excretion predicts imminent puberty in girls: a semi-longitudinal study.

PURPOSE: We explored the alternative of using overnight fold change in gonadotropin levels by comparing the last-night-voided (LNV) and first-morning-voided (FMV) urine concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as a conceptual analogy to the invasive gonadotropin-releasing hormone (GnRH) stimulation test setting. METHODS: We investigated the nocturnal changes in the immunoreactivity levels of urinary gonadotropins between early and late prepubertal stages as well as between early and late pubertal stages in FMV and LNV urine samples from 30 girls, of whom those who were prepubertal were further investigated through follow-up visits within the 1-year period from the start of the study. RESULTS: ROC analysis revealed that the FMV total U-LH and FMV U-FSH concentrations at or above 0.3 IU/L and 2.5 IU/L, respectively, were excellent predictors of forthcoming onset of puberty within 1 year (100% sensitivity, 100% specificity, AUC: 1.00, and n = 10, for both). FMV total U-LH concentration at or above 0.8 IU/L represented the cut-off for clinical signs of puberty. FMV/LNV total U-LH and FMV/LNV U-FSH ratios at or below 4.11 and 1.38, respectively, were also good predictors of the onset of clinical puberty within 1 year. An overnight increase (FMV/LNV ratio) in total U-LH concentrations and in the U-LH/U-FSH ratio at or below 1.2-fold in pubertal girls was associated with the postmenarcheal pubertal stage. CONCLUSION: FMV total U-LH and U-FSH above 0.3 IU/L and 2.5 IU/L, respectively, can be used as cut-off values to predict the manifestation of the clinical signs of puberty within 1 year. FMV total U-LH concentrations 0.3-0.8 IU/L and 0.6 IU/L may represent the range and the threshold, respectively, that reflect the loosening of the central brake on the GnRH pulse generator. An overnight increase of 20% or less in total U-LH concentrations and in the U-LH/U-FSH ratio in an early pubertal girl may serve as an indicator of imminent menarche, a presumed timing of which can be unraveled by future longitudinal studies.

Rare injury of the foot: Os trigonum fracture: A case report.

Os trigonum fractures are seen rarely. Our patient was a 16-year-old male patient who applied to our emergency service with right ankle pain due to acute hyperplantar flexion while playing football. There was a swelling on the right ankle and he had difficulty in walking. Os trigonum fracture was detected at lateral X-ray of the right ankle. No additional injury was detected with computed tomography and magnetic resonance imaging (MRI). Patient was treated conservatively. A short leg cast was applied. Cast was removed after six weeks and range of motion exercises were started. Union of fracture was seen on X-ray at six weeks from injury. Conservative treatment is thought to be a good option in these fractures. Computed tomography and MRI are important in the differential diagnosis and evaluation of additional injuries in this type of fracture.

Cytogenetic alterations induced by flupyradifurone, a new butenolide insecticide, in human lymphocytes.

Flupyradifurone (FPD), a member of the new class of butenolide insecticides, acts on nicotinic acetylcholine receptors. Studies on genotoxic and carcinogenic effects of FPD are very limited. This is the first study to investigate the cytotoxic and genotoxic effects of FPD and its metabolites on human lymphocyte cultures with or without a metabolic activation system (S9 mix) using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 85, 170, and 340 µg/ml of FPD in the presence (3 h treatment) and absence (48 h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. Statistically significant decreases were detected at the medium and highest concentrations for 48 h treatments while decreases in mitotic index (MI) in the presence of the S9 mix were found statistically significant at all FPD concentrations tested when compared with the solvent control. FPD also decreased the nuclear division index (NDI) at the highest concentration (340 µg/ml) in the absence of S9 mix. When compared with the solvent control, increases in CA frequencies were significant at the medium and highest concentrations. Significantly increased MN frequency was only found at the highest FPD concentration in cultures without S9 mix compared with the solvent control while increases in the MN frequencies in the presence of S9 mix were statistically significant at all FPD concentrations. The results of the present study indicate that FPD and its metabolites can show cytotoxic and genotoxic effects in human lymphocytes. More genotoxicity studies are necessary to make a possible risk assessment in humans.

Late onset of primary pulmonary primitive neuroectodermal tumor: a case report.

Lungs are one of most metastatic areas for primitive neuroectodermal tumor (PNET), however primary pulmonary PNET is extremely rare. Here we present a case of a 58-year-old male patient with a tumor in the right lung that originated from the lung but not from chest wall. Patient was diagnosed with PNET following histological and immunohistochemical examination of CT-guided percutaneous tru-cut needle biopsy and no distant metastasis were detected in PET-CT scan. As advised recently in published literature, surgical resection following neoadjuvant chemotherapy protocol is preferred in the treatment of our patient as it has better success of complete resection leading to higher 5-year survival rates. Although primary pulmonary PNET is uncommon, it should be taken into account and complete surgical resection should be aimed as treatment to achieve higher survival rates.

Comparison of Semi-Invasive "Internal Splinting" and Open Suturing Techniques in Achilles Tendon Rupture Surgery.

The goal of the present study was to evaluate the semi-invasive "internal splinting" (SIIS) method for repair of Achilles tendon rupture relative to open repair with Krakow sutures. Efficacy was evaluated based on the clinical and functional outcomes, postoperative magnetic resonance imaging measurements, isokinetic results, and surgical complication rates. Functional measurements included the Thermann and American Orthopaedic Foot and Ankle Society (AOFAS) ankle scores, bilateral ankle dorsiflexion, and plantar flexion measurements. Magnetic resonance imaging was used to compare the bilateral length and thickness of each Achilles tendon. The isokinetic outcomes were evaluated using a Biodex System 3 dynamometer. Of the 45 patients meeting the inclusion criteria, 24 were treated by SIIS and 21 by the open Krackow suture technique. The mean follow-up time for all patients was 43.7 (range 6 to 116) months. In the SIIS group, patients returned to normal daily activities after 7.2 (range 6 to 8) weeks compared with 14.3 (range 12 to 15) weeks in the open surgery group. The AOFAS ankle scores were 93.5 (range 82 to 100) points in the open repair group and 96.2 (range 86 to 100) points in the SIIS group. The Thermann scores were 80.4 (range 53 to 91) points for the open repair group and 87.9 (range 81 to 100) points for the SIIS method. The mean Achilles length on the operated side measured using magnetic resonance imaging was 175.06 (range 110 to 224) mm and 177.76 (range 149 to 214) mm for the open surgery and SIIS groups, respectively. Sensory impairment in the territory of the sural nerve was identified in 1 patient immediately after SIIS surgery, although this defect had completely resolved within 12 months. SIIS yielded better outcomes relative to the open surgery group according to the isokinetic measurements. Taken together, these data indicate the SIIS method for Achilles tendon ruptures performed better in terms of both functional and objective outcomes compared with open surgery.

Neurogenic differentiation capacity of subacromial bursal tissue-derived stem cells.

In this study, analysis and comprehensive comparison of neurogenic differentiation capacity of human bursal tissue-derived-stem cells (hBT-SCs) was aimed with human bone marrow derived mesenchymal stem cells (hBM-MSCs). hBT-SCs was isolated from subacromial bursa tissue (n = 3) by collagen type-II digestion. The expression of stem cell markers, differentiation capacity and telomerase activity were determined for both cell lines. The expression levels of neurogenic cell markers were compared consecutively. With respect to the surface marker profile, both cells display similar pluripotency phenotypes. Both cells successfully differentiated into osteo- and adipogenic cell lines. The immune staining of mesenchymal, stem cell and neurogenic markers gave positive reaction. The gene expression level for Tubb3, Nestin, Gfap, Map2, Nf-h, and Nf-l was higher in hBT-SCs than hBM-MSCs. The high level of neurotrophic factors, like Tenascin C, NGF, BDNF, VEGF, and CNTF might indicate their regeneration and maintenance capacity in damaged neural tissue. Besides they are alternative source for human mesenchymal stem cells, hBT-SCs assess the possibility to use in clinical studies.

The short- and long- term effects of estrogen deficiency on apoptosis in musculoskeletal tissues: an experimental animal model study.

BACKGROUND: Estrogen is the major sex steroid affecting the growth, remodeling, and homeostasis of the female skeleton. Estrogen loss in postmenopausal women leads to osteoporosis. The aim of this study was to evaluate the early and long- term effects of estrogen loss on bones, tendons, muscles, and menisci in ovariectomized rats.  METHODS: Fifteen rats were randomized into three groups of five animals each. The first group was the control group with no additional surgical procedure, but the rest (groups 2 and 3) were bilaterally ovariectomized . All animals in the group 2 were sacrificed at 14th week to evaluate the short- term effect, and all of other animals in the groups 1 and 3 were sacrificed at 28th week to analyze the long- term effect of estrogen loss in the ovariectomized group and to control with the group 1. Quadriceps muscles, Achilles tendons, menisci, and femur cortical bones from both lower extremities were taken. The amount of apoptosis was measured. RESULTS: There was a significant increase in cell apoptosis in bones, muscles, and tendons with insignificant increase in cell apoptosis in menisci at early and late periods in rats with ovariectomies than the control.  CONCLUSION: The results indicated that estrogen loss after ovariectomy does not only affect bones; it may also increase cell apoptosis in different tissues such as muscles, tendons, and menisci.

Anterior knee dislocation with ipsilateral open tibial shaft fracture: a 5-year clinical follow-up of a professional athlete.

Traumatic dislocation of the knee joint is an uncommon complex, multiple ligamentous injury resulting from a high-energy trauma. Significant lack of functions can be seen because of both early and late complications of these injuries such as popliteal artery disruption, peroneal nerve injury, persistent instability and posttraumatic arthritis. Therefore, the emergency surgery is necessary due to possibility of neurovascular compromise and limb loss. Controversies over operative versus closed immobilization of traumatic complex, multiple ligamentous knee injury are still debated. We report a case of traumatic anterior dislocation of the right knee with an ipsilateral tibial shaft fracture in association with right popliteal artery occlusion of a professional athlete who was returned to his sports activity by surgical treated tibia fracture and conservative treatment of the knee dislocation.

Modelo experimental de osteoporose: comparação entre ovariectomia e toxina botulínica tipo A / Experimental model of osteoporosis: comparison between ovariectomy and botulinum toxin A

OBJETIVO: Avaliar se a toxina botulínica tipo A (TB-A) tem efeito similar ao da ovariectomia (OVX) sobre os ossos com relação à densitometria mineral óssea.MÉTODOS: Um total de 51 ratas foi dividido randomicamente em três grupos de 17 animais cada. As ratas no primeiro grupo foram o controle, sem qualquer procedimento cirúrgico (Grupo 1). O Grupo 2 recebeu TB-A, enquanto o Grupo 3 foi submetido a OVX. Um total de 8 UI de TB-A foi injetado na região femoral direita de todas as ratas do Grupo 2. No início do estudo e 14 semanas depois, mediu-se a densidade mineral óssea (DMO) dos fêmures esquerdo e direito de todas as ratas em ambos os grupos.RESULTADOS: Não houve diferença estatisticamente significante entre os grupos com relação à DMO do início do estudo. Na 14ªsemana, a DMO dos fêmures direitos foi estatisticamente superior no Grupo 1 do que nos outros grupos, embora não houvesse diferença com significância estatística entre os Grupos 2 e 3. Os resultados médios da DMO dos fêmures esquerdos no Grupo 3 foram inferiores, com significância estatística, do que os resultados dos Grupos 1 e 2 na 14ª semana.CONCLUSÃO: Os resultados do presente estudo mostraram que a TB-A teve efeito similar ao da OVX sobre a osteoporose, no que diz respeito à DMO. Nível de Evidência I, Estudo Experimental, Controlado em Animais.

OBJECTIVE: To evaluate whether Botulinum toxin-A (BTX-A) has a similar effect to that of ovariectomy (OVX) on bone regarding bone mineral densitometry.METHODS: A total of 51 female rats were randomly divided into three groups of 17 animals each. The rats in the first group formed the control group, without any surgical procedure (Group 1). Group 2 received BTX-A while Group 3 was subjected to OVX. A total of 8 IU of BTX-A was injected into the right femoral region of all rats in Group 2. At baseline and 14 weeks later, bone mineral densities (BMD) of the left and right femurs of all rats in both groups were measured.RESULTS: There was no statistically significant difference between the groups with respect to baseline BMD. At the 14th week the BMD of the right femurs were statistically significantly higher in Group 1 than other groups, although there was no statistically significant difference between Groups 2 and 3. The mean BMD results of the left femur in Group 3 were statistically significantly lower than the results in Groups 1 and 2 at the 14th week.CONCLUSION: The results of the current study showed that BTX-A had a similar effect to that of OVX on osteoporosis regarding BMD. Evidence Level I, Experimental, Controlled, Animal Study.

Comparison of superoxide dismutase, glutathione peroxidase and adenosine deaminase activities between respiratory and nocturnal subtypes of patients with panic disorder.

OBJECTIVE: There is mounting evidence indicating that oxidative and inflammatory processes may have an important role in the pathogenesis of panic disorder (PD). PD is a heterogeneous disease, and panic attacks are divided according to the different symptom clusters as respiratory, nocturnal, non-fearful, cognitive, or vestibular subtypes. The aim of this study was to compare whole-blood and serum superoxide dismutase (SOD), glutathione peroxidase and adenosine deaminase activities in PD patients with/without nocturnal, respiratory subtypes and healthy subjects. METHODS: The study was conducted including 60 patients with PD and 30 healthy control subjects. The Panic Attack Symptom Checklist, Panic and Agoraphobia Scale, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were administered to the patients. Biochemical analyses were performed after all the blood samples were collected. RESULTS: We found that whole-blood SOD and glutathione peroxidase activities of patients were significantly lower and adenosine deaminase activities of patients were higher than those of healthy controls. There were no statistically significant differences between respiratory and nocturnal subtypes. In addition, there were no marked relationships between the duration of illness and panic-agoraphobia scores of patients with nocturnal subtypes. Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores of patients with the nocturnal subtype were markedly higher than those of patients without the nocturnal subtype. CONCLUSION: The results suggest that oxidative and inflammatory processes may play a role in the pathophysiology of PD. These findings may support the idea that both nocturnal and respiratory subtypes of PD have different symptom clusters of the same disease.

Oxidative stress in patients with primary insomnia.

OBJECTIVE: Many physiological and pathological processes, such as infections, environmental toxins, and ionizing radiation increase bodily concentrations of oxidizing substances, known as free radicals, which lead to neurodegenerative disorders. Sleep is one of the most important factors contributing to health; however, insomnia is among the most prevalent health complaints. METHODS: In this study, for the first time in the literature, we investigated the effects of primary insomnia on certain oxidative stress biomarkers. For this purpose, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were measured in 30 patients with primary insomnia and 30 healthy volunteers RESULTS: Our results show that the patients with primary insomnia had significantly lower GSH-Px activity and higher MDA levels compared with the controls. CONCLUSION: These results may indicate the important role of sleep in attenuating oxidative stress.

Hormones and cytokines in childhood obesity.

OBJECTIVE: Obesity is a growing worldwide health problem affecting both adults and children. Effective prevention and treatment modalities can be achieved by understanding the pathogenesis of obesity better. This review addresses some of the issues related to the hormones and cytokines taking part in the pathogenesis of obesity, energy balance and inflammation. DESIGN: We reviewed current literature on this broad subject especially concentrating on the functions of the hormones and cytokines taking part in the pathogenesis of the childhood obesity. Using the key words obesity, children, hormones, cytokines publications and cross references were evaluated from PubMed database between 1957 and 2009. RESULTS: In children, leptin and ghrelin are two hormones which have major influence on energy balance. Leptin is responsible from long term regulation of energy balance and ghrelin functions as an appetite stimulatory signal. In contrast to ghrelin, obestatin acts as an anorexigenic hormone by suppressing food intake. Adipokines secreted from adipose tissue are the key regulators of inflammation in obesity. Increased TNF-alpha and IL-6 levels but decreased levels of adiponectin and IL-10 are associated with increased inflammation, tissue injury and complications of obesity. CONCLUSIONS: Development, pathogenesis and complications of childhood obesity consist of complex mechanisms including numerous cytokines and hormones. New treatment modalities depend on understanding these complex mechanisms.

Thyroxine-induced hypermotor seizure.

Thyroxine-induced epilepsy is a very rare condition occurring in epileptic patients. Here we report a boy with thyroxine-induced hypermotor seizure (HMS) following thyroxine administration for his central hypothyroidism secondary to surgery and cranial radiation for his brain tumor. After 3 years seizure-free period, he had repeated HMS, seven to eight attacks per day, after initiation L-thyroxine treatment. Following reduction of the daily thyroxine dose, his seizures decreased in frequency. To our knowledge, this is the first reported case of HMS associated with L-thyroxine administration.

Erythropoietin exerts neuroprotective effect in neonatal rat model of hypoxic-ischemic brain injury.

Hypoxic-ischemic encephalopathy seen in survivors of perinatal asphyxia is a frequently encountered and a major clinical problem for which there is currently no effective treatment. Hematopoietic neuroprotective agents, such as erythropoietin (EPO) may rescue neurons from cell death in this setting. EPO is a cytokine hormone that has neuroprotective effect in vitro and in vivo. In this study, we evaluated the effect of posthypoxic EPO administration in an animal model of neonatal hypoxic-ischemic injury. Our results show that a single intracerebroventricular injection of EPO immediately after hypoxic-ischemic insult in neonatal rat model of hypoxic-ischemia reduced the extent of hypoxic-ischemic brain damage. The mean infarct volume assessed 7 days after hypoxia was significantly smaller in EPO-treated group than in the control group. These findings suggest that EPO may provide benefit after hypoxic-ischemic events in the developing brain, a major contributor to static encephalopathy and cerebral palsy.