Transient demineralization of the hip--case report]

Transient osteoporosis of the hip is an uncommon disorder of unclear etiology. It is often confused with other diagnosis including osteonecrosis of the femoral head. Authors describe a case of transient osteoporosis of the hip of 32 years woman. The symptoms occurred in third trimester of pregnancy. The primary symptoms were right hip pain and decreased range of motion of the right hip. In diagnostic process helpful were clinical examination, X-ray, ultrasonography, MRI and microscopic examination. As a treatment authors used walking on crutches, calcitonin and calcium preparate. After a few months remission of symptoms and normalization in accessory investigations were obtained.     

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.     

Leptin levels as function of age, gender, auxological and hormonal parameters in 202 healthy neonates at birth and during the first month of life

Leptin signals to the brain energy stores and balance while integrating neuroendocrine functions. Leptin levels in adults are higher in females than in males, while a gender-related difference in newborns is controversial. To clarify this point, in 202 healthy neonates we measured dynamic changes in leptin levels over the first month of life and looked for correlation between leptin levels and auxological and hormonal parameters. Cord leptin concentration in females was higher (p < 0.001) than in males. IGF-I, IGF-II, insulin, testosterone and 17beta-estradiol levels were similar in both sexes while insulin-like growth factor binding protein 3 (IGF-BP3) levels in females were slightly higher than in males. Leptin levels were positively associated to body weight, gestational age, IGF-BP3 levels, insulin levels and maternal body mass index (BMI) at time of delivery. In a subset of subjects (no. = 65), in comparison with cord levels, serum leptin levels were decreased on the 5th day of life (p < 0.0001) and then increased at 1 month (p < 0.0001). Positive association between leptin and weight was lost on the 5th day of life but present again at 1 month. In conclusion, our findings in a large population of neonates definitely show that leptin levels at birth are functions of gender, body weight and gestational age but not of length, cranial circumference, IGF-I and IGF-II levels. These findings, coupled with weight-independent prompt decrease after birth followed by weight-dependent increase at one month of life, suggest that leptin secretion in neonates as well as in adults mainly signals the nutritional state to the brain.     

Circulating ghrelin levels in the newborn are positively associated with gestational age

OBJECTIVE: Ghrelin exerts potent GH-releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. Newborns are characterized by GH hypersecretion associated with low IGF-I levels reflecting peripheral GH resistance. STUDY DESIGN: The aim of our study was to measure cord ghrelin levels in 117 newborns appropriate for gestational age, born either at term or preterm. RESULTS: Ghrelin levels in cord blood (median; 25th-75th centile: 327.6; 206.0-413.0 pg/ml) were higher (P < 0.0001) than those in maternal blood at delivery (133.0; 89.0-173.7 pg/ml), without gender differences. A positive correlation between ghrelin levels in mothers and newborns (r = 0.26, P < 0.01) was observed. Ghrelin levels in newborns born at term (399.0; 229.0-438.0 pg/ml) were remarkably higher (P < 0.0001) than those in born preterm (208.0; 144.5-278.9 pg/ml). A clear positive association was present between ghrelin levels and gestational age. No association between ghrelin and GH, IGF-I, insulin, glucose and leptin levels were found. CONCLUSIONS: Cord ghrelin levels show clear gestational age-related dependency. The lack of any direct relationship between ghrelin and anthropometric or biochemical parameters in adequate for gestational age newborns does not support the hypothesis that ghrelin has major role in foetal GH secretion and growth.     

Therapeutic Biomarkers in Lung Neuroendocrine Neoplasia

The well-known classification of neuroendocrine neoplasms of the lung into four major subtypes (including typical and atypical carcinoids and small- and large-cell neuroendocrine carcinomas) has a proven prognostic validity but only partially helps to predict the response to specific therapies. Therapeutic biomarkers are incompletely known and include morphological, immunophenotypic, and molecular markers. Morphology alone has no specific predictive role, nor has any immunophenotypic marker been proven to bear predictive implications. Ki67 is a relevant prognostic marker and can indirectly predict response to chemotherapy, when levels are extremely high in high-grade neuroendocrine (NE) carcinomas. The expression of somatostatin receptors, especially of the type 2A, has been shown to predict response to somatostatin analog treatments, paralleling the information derived from octreotide scintigraphy. mTOR pathway is targeted by specific inhibitors, but the exact cellular molecules predicting response are still to be defined. It seems that high levels of phosphorylated forms of mTOR and of its downstream factor S6K are associated to a better response to rapalogs in experimental models. Data from gene expression profiling and mutational analyses are currently emerging, providing a more detailed map of different molecular activation pathways, potentially leading to a more accurate molecular classification of lung NE tumors as well as to the discovery of new therapeutic targets. The combination of mutational profiles with those of upregulated or downregulated genes also by gene gains or losses may ultimately provide a better characterization of NE tumor histological types in terms of response to specific chemotherapy or biotherapy.     

The importance of erythroid expansion in determining the extent of apoptosis in erythroid precursors in patients with beta-thalassemia major

Beta-thalassemia major is characterized by ineffective erythropoiesis leading to severe anemia and extensive erythroid expansion. The ineffective erythropoiesis is in part due to accelerated apoptosis of the thalassemic erythroid precursors; however, the extent of apoptosis is surprisingly variable. To understand this variability as well as the fact that some patients undergoing allogeneic marrow transplantation are resistant to the myeloablative program, we attempted more quantitative analyses. Two groups of patients totaling 44 were studied, along with 25 healthy controls, and 7 patients with hemolysis and/or ineffective erythropoeisis. By 2 flow cytometric methods, thalassemic erythroid precursors underwent apoptosis at a rate that was 3 to 4 times normal. Because thalassemic marrow has between 5- to 6-fold more erythroid precursors than healthy marrow, this translated into an absolute increase in erythroid precursor apoptosis of about 15-fold above our healthy controls. In searching for the causes of the variability in thalassemic erythroid precursor apoptosis, we discovered tight direct correlations between the relative and absolute extent of apoptosis and the extent of erythroid expansion as measured either by the absolute number of marrow erythroid precursors or by serum soluble transferrin receptor levels. These results could mean that the most extreme rates of erythroid proliferation lend themselves to cellular errors that turn on apoptotic programs. Alternatively, extreme rates of erythroid hyperplasia and apoptosis might be characteristic of more severely affected patients. Lastly, extreme erythroid hyperplasia could generate such numbers of apoptotic erythroid precursors that marrow macrophages are overwhelmed, leaving more apoptotic cells in the sample.     

Usefulness of Helicobacter pylori stool antigen test to monitor response to eradication treatment in children

BACKGROUND: The monitoring of the results of eradication treatment is a crucial step for patients with Helicobacter pylori gastritis. A non-invasive test for H. pylori antigens in stools (HpSA) was recently validated for children. AIM: To evaluate the accuracy of HpSA in monitoring eradication treatment in children. METHODS: In 60 children, H. pylori gastritis was diagnosed by endoscopy and the 13C-urea breath test. The children were treated and returned for a follow-up (13)C-urea breath test 6 weeks after the end of treatment. Children were considered cured when the (13)C-urea breath test was negative. Stool were collected at baseline, and at 2 and 6 weeks. Stool antigens were measured by HpSA. RESULTS: According to (13)C-urea breath test, 6 weeks after the end of treatment 49 children were cured and 11 were still H. pylori-positive. The sensitivity and specificity of HpSA on stools collected 2 weeks after therapy were 100%. At 6 weeks specificity was 93.9 and sensitivity 100%. Results by visual reading were concordant with the plate-reader in all but two cases at baseline. CONCLUSIONS: HpSA is accurate for monitoring treatment in children as early as 2 weeks after therapy, when information is most useful and unachievable with other tests. Results by visual reading are accurate, and this can make the test cheaper and more practical.