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Kingella kingae is a bacterium that colonizes the upper respiratory tract. Despite its low pathogenicity in this location, previous respiratory pathological processes may favor its systemic spread causing bone and joint infections, mainly in children under five years. It can be considered an emerging pathogen in osteoarticular infection in pediatric patients. We report the case of a two-year-old girl with hips pain and limitation of both abduction and extension, and fever. Radiography and ultrasonography were compatible with transitory synovitis; showed scintigraphy inflammatory pathology of the right hip. Articular puncture was performed. The material showed altered biochemical parameters. Microbiological culture yielded isolation of a strain of K. kingae susceptible to beta-lactam antibiotics, azithromycin and trimethoprim-sulfamethoxazole. Blood cultures were negative. The patient was treated empirically with cloxacillin and cefotaxime iv. and continued with amoxicillin-clavulanate orally with osteoarticular improvement.

Purpose of Review: In the last years, interesting advances have been reported in the treatment of infrequent digestive tumors. The increasing development of new targeted therapies in human cancer has also impacted in these rare gastrointestinal malignancies providing a wide range of possibilities in the design of future clinical trials., Recent Findings: The inhibition of angiogenesis and the blockage of the epidermal growth factor receptor pathway have provided the most interesting activity in recently reported studies for esophageal and biliary tract carcinomas. Additionally, several targeted therapies have been developed to target the main kinase proteins of the most important pathways of these malignancies. The results of the biggest phase III trial in locally advanced anal carcinoma have been recently published. Finally, the inhibition of epidermal growth factor receptor has also showed promising activity in anal carcinomas., Summary: Recent advances in the knowledge of molecular mechanism of carcinogenesis have led to meaningful changes in the management of gastrointestinal cancers. Although the major advances in targeted therapy have been introduced in the treatment of colorectal cancer, new interesting approaches have been reported in less frequent gastrointestinal tumors such as esophageal, biliary tract, and anal canal carcinoma opening a new hope in the treatment of these rare tumors in the molecular targeted therapy era.

Although the prognosis of cancer remains poor recent advances in the diagnostic methods, new approaches in surgical procedures and the development of new therapeutic agents have had a significant impact in the outcome of cancer patients. A better understanding of the molecular pathways that characterize cell growth, apoptosis, angiogenesis and invasion has provided novel targets in cancer therapy. The epidermal growth factor receptor (EGFR) mediated signal transduction has been one of the most studied pathways in carcinogenesis. The phosphorylation of EGFR activates multiple biological processes including apoptosis, differentiation, cellular proliferation, motility, invasion, adhesion, DNA repair and survival. Several therapies have been developed to inactivate the EGFR pathway including monoclonal antibodies against the extracellular domain of EGFR. In this review, the authors examine the development of monoclonal antibodies against EGFR and the effects of this blockage in cell cycle, as well as the most important trials with these monoclonal antibodies in several tumor types.

Objectives: The utility of many molecules as tumor markers in melanoma has been investigated with different results. The aims of this study was to compare the value of tyrosinase mRNA by reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood and of serum S-100 protein in patients with melanoma at different stages of disease., Methods: We have studied 90 peripheral blood samples corresponding to 90 patients that had been diagnosed with melanoma. The clinical staging at the time of blood sampling was performed according to the American Join Committee on Cancer guidelines. S-100 protein in serum was measured by enzyme-linked immunosorbent assay (normal range: 0-0.150 microg) and the presence of tyrosinase mRNA was assessed by RT-PCR., Results: Median progression-free survival was 281 days for tyrosinase positive patients and it has not been reached for tyrosinase negative patients (P = 0.03). Median progression free survival was 213 days for patients with elevated serum S-100 and it has not been reached for patients with normal level of serum S-100 (P < 0.001). Median overall survival (OS) was 396 days for tyrosinase positive patients and it has not been reached for negative patients (P = 0.0096). Median OS was 282 days for patients with elevated serum S-100 and it has not been reached for patients with normal level of serum S-100 (P < 0.001). In a multivariate analysis, both markers have significant prognostic value for time to progression and for survival (chi(2) test)., Conclusions: RT-PCR for tyrosinase mRNA and S-100 are significant prognostic factors for progression-free survival and OS in melanoma. S-100 has higher sensitivity and specificity than tyrosinase.

We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.

We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

Introduction: Patients with any type of congenital metabolism error are at risk for developing osteoporosis. To gain further insight into the physiopathology of this disease, we studied bone mineral turnover in 10 children with hyperphenylalaninemia, seven with phenylketonuria and six with galactosemia. Oral intake was strictly controlled and the children followed recommendations for physical exercise., Material and Method: Markers of bone resorption (hydroxyproline and pyridinoline in urine samples) and markers of bone formation (levels of osteocalcin and C-terminal procollagen peptide type I) were analyzed. Bone mineral density was analyzed by ultrasound densitometry., Results: A non-significant reduction in bone densitometry with respect to the normal population was observed. Bone mineral turnover was slightly diminished in patients with phenylketonuria but was within the normal range in patients with hyperphenylalaninemia and galactosemia., Conclusion: Adequate control of dietary intake of both proteins and minerals, as well as a healthy lifestyle, can prevent the development of significant alterations in bone mineralization.

Objective: To determine the normal profile of bone turnover markers in childhood in order to enable evaluation of bone mineralization status in the healthy pediatric population and in the population at risk of osteoporosis., Patients and Methods: A population of 75 healthy children aged between 6 months and 14 years was studied. Levels of osteocalcin and C-terminal procollagen peptide type I, as markers of bone apposition, were determined in serum. Levels of hydroxyproline and pyridinoline, as markers of bone resorption, were determined in urine samples. Statistical analysis of the results was performed., Results: The highest levels of the four markers were obtained in the first 4 years of life. Markers of bone resorption showed a continuous statistically significant decrease until the age of 14 years (p < 0.05), whereas markers of bone apposition decreased slightly after the age of 4 years and then remained stable until the age of 14 years., Discussion: These findings are compatible with the presence of intense bone turnover in the first 4 years of life and with a predominance of the phenomenon of bone apposition throughout the first 14 years of life. Knowledge of the normal profile of these markers allows evaluation of bone mineralization status in the healthy pediatric population and in the population at risk of osteoporosis.

Congenital adrenal hyperplasia is a general term applied to several disorders caused by inherited recessive defects of cortisol synthesis. The most common form is 21-hydroxylase deficiency, accounting for 95% of cases. The classical forms have an incidence of one in 15,000 and the non-classical forms about one in 1,000. The classical or severe phenotype presents in the newborn period or early infancy with virilization and adrenal insufficiency, with or without salt-losing; the non-classical or mild phenotype presents in late childhood or early adulthood with signs of hyperandrogenism. This wide range of clinical expression is explained by genetic variation. Although there is a certain amount of genotype-phenotype correlation, discrepancies have been described. During the last 30 years there has been a substantial improvement in diagnosis and treatment of this disease, and patients with CAH now reach adulthood. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace glucocorticoids and mineralocorticoids as physiologically as possible. Clinical management is often complicated by periods of inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. Long-term consequences in adult life may include short stature, obesity, diminished bone mass, gonadal dysfunction with low fertility rates and psychosexual dysfunction in females. New treatment approaches are under investigation, such as the use of anti-androgens, inhibitors of estrogen production and adrenalectomy for severely resistant cases.

Objective: Our aim was to know the long-term effects of treatment with LHRH analogs on the bone mass of patients with precocious or advanced puberty., Patients and Methods: Forty-six patients (11 boys and 35 girls) received a-LHRH throughout a 2-year period. The diagnoses were precocious or advance puberty alone or associated to other pathologies. The bone mass was indirectly estimated by measuring the cortical thickness (CT) and the metacarpal diameter (BD) of the 2nd, 3rd, and 4th metacarpals, taking as a reference values the results of the longitudinal Aragonese study of the "Andrea Prader" Center., Results: The CT was 1.3 SD at the beginning and decreased to 0.3 SD (p < 0.002) by the end of therapy and continuing losing to reach 0.1 SD after withdrawal. The BA decreased from 0.8 SD to 0.7 SD (p < 0.0002) and continued decreasing to reach 0.5 SD after withdrawal (p < 0.05). The BD went from -0.64 to -0.62 and to -0.9 SD (p < 0.04) after withdrawal. The longitudinal study of the same 18 cases gave similar results. No significant difference was found between sexes., Conclusions: In precocious or advance puberty, the bone age and the cortical thickness are increased. After two years of treatment with a-LHRH both decreased significantly and stabilized one year after its suppression. The BD does not change during the treatment, but continues losing value thereafter. This loss of bone mass, not well known in this pediatric situation, is probably related to estrogen deprivation and needs the attention of the physician in order to take possible preventative measures.