Long-term response in biochemical markers of bone turnover during enzyme replacement therapy in a case-series of patients with Gaucher disease type I from Northern Greece.

BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder characterized by severe skeletal complications. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. The objective of this case series was to analyze the long-term effect of enzyme replacement therapy on chemokines MIP-1a and MIP-1b, cytokines IL-3, IL-6, IL-10, and IL-12, osteoprotegerin (OPG) and osteocalcin (BGP), chitotriosidase, quantitative ultrasound sonography (QUS), bone magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) in patients with GD in Northern Greece. In addition, the study aimed in investigating possible relationship between the above mentioned parameters. PATIENTS AND METHODS: Seven patients with GD type I (three males and four females) were included in the study. Mean age was 26.29 ± 15.34 years (range 7-47 years). Six patients were receiving enzyme replacement therapy (ERT), with 40-60 IU/kg of imiglucerase weekly, for a mean period of 36 months prior to study initiation. One patient started ERT after his inclusion in the study. The levels of MIP-1a, MIP-1b, IL-3, IL-6, IL-10, IL-12, OPG, BGP, chitotriosidase, bone imaging parameters assessed with two different techniques (QUS and DXA) and MRI data were estimated at baseline (T0) and after two years on ERT. RESULTS: Chitotriosidase, MIP-1a, and IL-6 levels decreased in all patients after two years of ERT (p =0.05). In contrast, OPG and BGP levels increased (p =0.04 and p =0.02, respectively). Bone mineral density (BMD) demonstrated a progressive improvement with regards to the Z-score in all patients (p =0.05). The decrease in the plasma levels of MIP-1a strongly correlated with a decrease in the plasma levels of chitotriosidase. Additionally, decreased plasma levels of IL-6 were correlated with increased Z-score both at baseline (T0) as well as two years later, in all patients. There was no correlation between MRI findings and any inflammatory biomarker. CONCLUSIONS: Measurement of serum markers in patients with GD under ERT could be used as an auxiliary tool in the monitoring of bone involvement, in combination with MRI imaging and BMD. However, larger studies involving higher numbers of GD patients are needed to confirm these conclusions. Hippokratia 2016, 20(2): 153-159.

A 2-year prospective densitometric study on the influence of Fok-I gene polymorphism in young patients with thalassaemia major.

UNLABELLED: This study is to estimate the degree of genetic contribution of Fok-I gene polymorphism of Vitamin D receptor to bone mass in patients with thalassaemia. Results indicate a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young thalassemic patients. INTRODUCTION: The purpose of this study is to estimate prospectively the degree of genetic contribution of Fok-I gene polymorphism of vitamin D receptor (VDR) to the evolution of bone mass in patients with beta-thalassemia major (b-TH). METHODS: Sixty-four children and young adults (33 males and 31 females) with mean decimal age of 23.20 ± 5.41 (range 9.25-32.41 years) were recruited in this study. All patients were genotyping for Fok-I gene polymorphism and were assessed with dual energy X-ray absorptiometry (DXA) at baseline and 2 years after. Z-scores were calculated based on normal age and sex matched Caucasian population. Metabolites of vitamin D, intact PTH, total calcium, inorganic phosphorous, and alkaline phosphatase were measured at the serum pre-transfusion. RESULTS: A moderate proportion of patients had decreased DXA Z-scores (Z-score ≤-2) predominately in total hip (31 %) and secondary in lumbar spine (15.6 %). Patients being homozygous for the f allele had apparently higher BMD Z-scores compared with those carrying the F allele in homo- or heterozygosity, however, with a difference that did not reached significance. Interestingly enough, a significant deterioration in BMD Z-scores measured at femur (FF: P = 0.004 Ff: P < 0.001, ff: P = 0.024) and total hip (FF: P = 0.022, Ff: P = 0.005) was recorded for all type of genotypes, except for ff genotype and with regard to the total hip DXA values. An increased prevalence of serum 25(OH)D3 deficiency (59.4 %) and 25(OH)D3 borderline (12.5 %) was recorded. CONCLUSION: Our study indicates a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young patients with b-TM.

Clonidine and glucagon stimulation for testing growth hormone secretion in children and adolescents: can we make it with fewer samples?

BACKGROUND: Our aim was to retrospectively evaluate the possibility to reduce the number of GH analyses during clonidine and glucagon tests without compromising accuracy. SUBJECTS AND METHODS: Two hundred and forty-five tests were performed in a total of 188 children and adolescents with a mean age of 9.93 ± 2.88 yr in a single center during the last 5 yr. RESULTS: Ninety-one out of 158 (57.59%) clonidine tests and 47/87 (54.02%) glucagon tests had at least one sample >10 µg/l (negative). For clonidine tests, not measuring GH at 30 min would have resulted in only one negative test missed (0.63% false positive result), whereas not measuring GH both at 0 and 30 min would have increased the false positive percentage to 2.53%. Ending clonidine tests at 90 min would have resulted in 7 negative tests missed (4.43% false positive results). For glucagon tests, more than half of the tests peaked at 120 min (56.32%). Skipping sampling at 0, 60 and 180 min provided a false positive rate of 5.75%. CONCLUSIONS: For clonidine tests we can omit blood sampling at time points 0 and 30 min without significantly compromising accuracy.

Defining overweight and obesity among Greek children living in Thessaloniki: International versus local reference standards.

BACKGROUND: Body Mass Index (BMI) offers a simple and reasonable measure of obesity that, with the use of the appropriate reference, can help in the early detection of children with weight problems. Our aim was to compare the two most commonly used international BMI references and the national Greek BMI reference in identifying Greek children being overweight and obese. METHODS: A group of 1557 children (820 girls and 737 boys, mean age: 11.42 ± 3.51 years) were studied. Weight and height was measured using standard methods, and BMI was calculated. Overweight and obesity were determined using the International Obesity Task Force (IOTF) standards, the Centers for Disease Control and Prevention (CDC) BMI-forage curves and the most recent Greek BMI-for-age curves. RESULTS: RESULTS showed that the IOTF's cut-off limits identifies a significantly higher prevalence of overweight (22.4%) compared with both the CDC's (11.8%, p=0.03) and the Greek's (7.4%, p=0.002) cut-off limits. However, the prevalence of obesity was generally increased when it was determined using the CDC's cut-off limits (13.9%) compared to the prevalence calculated with both the IOTF's (6.5%, p=0.05) and the Greek's (6.9%, n.s.) cut off limits. CONCLUSIONS: The use of the national Greek reference standards for BMI underestimates the true prevalence of overweight and obesity. On the contrary, both the IOTF and the CDC standards, although independently, detect an increased number of overweight and obese children and thus they should be adopted in the clinical practice for an earlier identification and a timelier intervention.

Comparative study of dual energy X-ray absorptiometry and quantitative ultrasonography with the use of biochemical markers of bone turnover in boys with haemophilia.

Our aim was to evaluate bone status in boys with haemophilia using dual energy X-ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition, to compare these two methods with the use of biochemical markers of bone turnover. Twenty-six boys with a mean decimal age of 12.08 ± 4.44 years were included in the study which included a DXA scan at lumbar spine and radial, as well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor κB ligand (sRANK-L), osteoprotegerin (OPG) and osteocalcin (OC) were measured and joint evaluation was performed using the Hemophilia Joint Health Score (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone mineral density (BMD) Z-scores < -2, and 4 patients (15.4%) had BMD Z-scores between -1 and -2. Only one patient had radial and other two had tibial QUS Z-scores < -2. No agreement was recorded between QUS and DXA in identifying patients at risk for osteoporosis (k = 0.275, P = 0.063). Haemophiliacs had significantly higher serum levels of sRANK-L (21.04 ± 4.78 vs. 18.58 ± 2.28 ng mL(-1), P = 0.038) and of OC (5.35 ± 2.29 vs. 3.09 ± 0.61 ng mL(-1), P = 0.002) and significantly decreased levels of OPG (15.78 ± 2.53 vs. 23.79 ± 4.39 pg mL(-1), P < 0.001) compared with controls. QUS Z-scores at tibia significantly correlated with HJH Scores (r = -0.450, P = 0.040), whereas lumbar BMD Z-scores significantly correlated with body mass index Z-scores (r = 0.500, P = 0.009). More studies are warranted to identify the most accurate densitometric method for assessing bone status in haemophiliacs.

Evaluation of pelvic ultrasonography in the diagnosis and differentiation of various forms of sexual precocity in girls.

OBJECTIVES: This study was conducted to assess the role of pelvic ultrasound variables in discriminating between normal girls and girls with different forms of sexual precocity, and to establish reliable cut-off limits of pelvic ultrasound measurements for differentiating between these conditions. METHODS: Eighty-eight girls with different forms of sexual precocity (23 with premature thelarche, 15 with premature pubarche and 50 with central precocious puberty) were enrolled. All diagnoses were based on clinical examination with confirmation using the gonadotropin-releasing hormone-stimulation test. Additionally, 81 prepubertal girls, aged 0-10 years, were included as a control group. For statistical analysis and to facilitate comparisons, the groups were subdivided by age intervals (0-6, > 6-8 and > 8-10 years). All subjects underwent pelvic ultrasound examination for the measurement of uterine length, uterine volume, ovarian volume and the anteroposterior diameter at the fundus divided by the anteroposterior diameter at the cervix (fundal/cervical ratio, (F/C)). Finally, the morphological appearance of the ovaries was assessed. RESULTS: Patients with central precocious puberty had significantly higher values for all the ultrasound variables (with the exception of uterine length in the 1-6-year age group) in comparison to normal girls. Patients with premature thelarche and patients with premature pubarche showed similar pelvic ultrasound parameters to those of normal girls. Ovarian volume was the best parameter for identifying patients with central precocious puberty (a cut-off of 3.04 cm(3) had a sensitivity of 100% and a specificity of 97.1% for age interval 0-6 years, a cut-off of 3.35 cm(3) had a sensitivity of 100% and a specificity of 89.5% for age interval > 6-8 years, and a cut-off of 4.46 cm(3) had a sensitivity of 80.8% and a specificity of 88.5% for age interval > 8-10 years). Uterine length was the best parameter for distinguishing between patients with central precocious puberty and patients with premature thelarche (a cut-off of 3.185 cm had a sensitivity of 85.7% and a specificity of 91.7% for age interval 0-6 years, and a cut-off of 3.83 cm had a sensitivity of 82.4% and a specificity of 90.9% for age interval > 6-8 years). CONCLUSIONS: Ultrasound examination of the uterus and ovaries could serve as a complementary tool for the diagnosis of central precocious puberty and, consequently, for the early initiation of appropriate treatment.

Acute eosinophilic pneumonia: radiologic and clinical features.

PURPOSE: To determine the radiographic and computed tomographic (CT) characteristics of acute eosinophilic pneumonia. MATERIALS AND METHODS: Twelve consecutive patients with acute eosinophilic pneumonia were included in the study. The diagnosis was based on clinical symptoms and results of bronchoalveolar lavage. Plain chest radiographs were obtained in all patients; CT scans were obtained in three patients. Two thoracic radiologists reviewed the radiographs and CT scans. RESULTS: Ten patients had bilateral areas of air-space opacity on images obtained at presentation; in seven of these patients, interstitial areas of opacity were also present. Two patients had bilateral interstitial areas of opacity and no areas of air-space opacity. Interlobular septal thickening and ground-glass attenuation were present on CT scans in two patients; patchy bilateral consolidation was present on CT scans in one patient. Pleural effusion was present on radiographs in seven patients (58%) and was bilateral in five. Pleural effusion was present at some point during the course of disease in all patients. In all patients, air-space disease markedly improved within 3 days of initiation of treatment with corticosteroids. CONCLUSION: Acute eosinophilic pneumonia should be considered as a possible diagnosis when a previously healthy person presents with acute respiratory failure of unknown origin.

Acute eosinophilic pneumonia. A summary of 15 cases and review of the literature.

Idiopathic acute eosinophilic pneumonia (AEP) is an acute febrile illness that may be mistaken for an infectious pneumonia. Patients are often young and otherwise healthy. Clues to considering this disorder in a differential diagnosis include the acuity and severity of the clinical presentation and an initial chest X-ray with diffuse infiltrates, often interstitial, and the presence of Kerley B lines and/or evidence of pleural fluid. The diagnosis can be made through examination of bronchoalveolar lavage fluid in most cases, with careful exclusion of other similar eosinophilic lung disease. Although it can lead to life-threatening respiratory failure, AEP is easily treatable with corticosteroids. This disease has not been reported to recur in any patients to this point.

Tumors of the osseous spine: staging with MR imaging versus CT.

Twelve patients with tumors involving the osseous spine were evaluated with magnetic resonance (MR) imaging and computed tomography (CT), six with and six without intrathecal injection of contrast material. MR imaging was found to be superior to CT without contrast material and equal to CT with contrast material in delineating the anatomic relationships of the tumors, including bone involvement, spinal canal invasion, paraspinal soft-tissue extension, and vascular involvement. Since MR imaging can provide most of the anatomic information necessary for treatment planning, intrathecal injection of contrast material can be avoided in most instances when evaluating tumor involvement of the osseous spine. However, CT without contrast medium was superior to MR imaging in showing critical cortical bone destruction and calcified tumor matrix.

The knee: surface-coil MR imaging at 1.5 T1.

Seven normal knees (in five volunteers) and seven injured knees (in seven patients) were examined by high-resolution magnetic resonance (MR) imaging at 1.5 T with a surface coil. Seven medial meniscal tears, three anterior cruciate ligament tears, one posterior cruciate ligament avulsion, an old osteochondral fracture, femoral condylar chondromalacia, and one case of semimembranous tendon reinsertion were identified. MR images correlated well with recent double-contrast arthrograms or results of surgery. All tears were identified in both the sagittal and coronal planes. Because of its ability to demonstrate small meniscal lesions and ligamentous injuries readily, MR imaging with a surface coil may eventually replace the more invasive arthrography.

Intestinal transit time is delayed by artificial sphincters after massive enterectomy in dogs.

Artificial sphincters were created in three groups of dogs after the resection of 87.5 percent of the intestine in each animal. Intestinal transit time was measured after 6 weeks by observing the passage of a radiopaque medium through the animals' intestinal tracts. No statistically significant differences were found between the intestinal transit times of dogs with one artificial sphincter and control animals. In dogs with two artificial sphincters there was a delay in the radiologically monitored intestinal transit time that was statistically significant compared with that of the control group.

Meniscal tears: MR demonstration of experimentally produced injuries.

Magnetic resonance (MR) imaging was performed using a 1.5-T magnet on eight immature swine knees with surgically produced vertical and horizontal meniscal tears. Three radiologists, interpreting the images independently, detected all tears. Tears in the middle portion of the meniscus were best seen on sagittal views, while lesions of the anterior and posterior horns of the meniscus were best seen on coronal views. MR has several advantages over arthrography, the current diagnostic method for knee injuries: it is noninvasive, uses no ionizing radiation, and provides excellent soft-tissue contrast resolution.

Joint effusions: MR imaging.

Magnetic resonance (MR) images of the hips and knees of three healthy volunteers were reviewed and compared with images obtained from the hips of three patients with effusions. Comparison was also made with MR images obtained from two swine knees following the injections of saline in one and blood in the other. The anatomy of the knees and hips was well defined. The hip effusions were all easily recognized. MR images of the swine knees clearly demonstrated the experimentally produced joint effusions. The hip effusions and the experimentally introduced blood and saline all had long T1 and T2 values allowing easy differentiation from articular cartilage. We were unable to distinguish fresh blood from saline in the knee joints.

Posterior gastric artery and its significance as seen in angiograms.

The posterior gastric artery was detected angiographically in 46 or 100 patients (46 percent). The importance of radiologic detection of the presence or absence of this artery is emphasized, especially in surgical procedures related to the stomach and immediately adjacent structures.