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Isochromosome 18p is a rare chromosomal disorder that occurs with a frequency of approximately one in every 180,000 live births, and affects both genders equally. MOst cases result from a de novo formation. In the literature, there are currently only a small number of reports that describe the phenotypic and clinical features of Isochromosome 18p. In this article, we report six cases that displayed the phenotypic and clinical features of Isochromosome 18p, and which were subsequently confirmed by conventional karyotyping and fluorescence in situ hybridization. We also discuss the clinical features of these patients in the context of the cases previously reported in the literature.

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22q11.2 deletion syndrome is a pattern of malformations resulting from abnormalities during cephalic neural crest migration and during the development of the third and fourth branchial arch. It is also known as DiGeorge syndrome, as it is most often associated with a de novo 3 Mb hemizygous 22q11.2 deletion. The recognition of similarities and phenotypic overlap between DiGeorge syndrome and other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of this syndrome. Indeed, the extent of this phenotypic variability can often make it difficult to accurately diagnose DiGeorge syndrome. Tertiary monosomy resulting from the 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. In this report, we present a female infant with dysmorphic facial features, microcephaly, a cleft palate, unilateral membranous choanal atresia, convulsions, hypocalcemia, semilobar holoporencephaly and echocardiographic abnormalities. To the best of our knowledge, this is the first description of a newborn displaying both DiGeorge syndrome and deletion 18p syndromes.

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INTRODUCTION: There are approximately 800 different genomic alterations of the ß-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we have identified two novel putative mutations (HBB:c.*+108 A>G and HBB:c.*+132 C>T) in the 3' untranslated region (3'-UTR) of the ß-globin gene and describe their clinical implications. METHODS: Four patients from two unrelated families, all with hematological and clinical features associated with beta-thalassemia (ß-thal), and their family members were included. The molecular diagnoses of the ß-globin gene mutations were performed by direct sequencing. RESULTS: A novel mutation, HBB:c.*+108 A>G, was found in combination with the IVS-I-110 G>A (HBB:c.93-21 G>A) mutation in three siblings (two brothers and one sister) from one of the families involved in our study. Their mother was found to be a carrier for HBB:c.*+108 A>G with normal HbA2 levels. The other novel mutation, HBB:c.*+132 C>T, was found in combination with IVS-I-1 G>A (HBB:c.92 + 1G>A) in a 7-year-old boy diagnosed as ß-thal intermedia from the second family. His father and two brothers were all carriers of HBB:c.*+132 C>T with borderline HbA2 levels. CONCLUSION: Based on the observed ß-thal intermedia phenotypes and the accompanying mutations, we conclude that these novel ß-globin gene 3' UTR mutations are associated with the mild phenotype of ß-thal.

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BACKGROUND: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. OBJECTIVES: To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. SELECTION CRITERIA: All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. MAIN RESULTS: Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, p=0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy. AUTHORS' CONCLUSIONS: We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

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BACKGROUND: Acute lymphoblastic leukaemia (ALL) is the most common cancer in childhood and febrile neutropenia is a potentially life-threatening side effect of its treatment. Current treatment consists of supportive care plus antibiotics. Clinical trials have attempted to evaluate the use of colony-stimulating factors (CSF) as additional therapy to prevent febrile neutropenia in children with ALL. The individual trials do not show whether there is significant benefit or not. Systematic review provides the most reliable assessment and the best recommendations for practice. OBJECTIVES: To evaluate the safety and effectiveness of the addition of G-CSF or GM-CSF to myelosuppressive chemotherapy in children with ALL, in an effort to prevent the development of febrile neutropenia. Evaluation of number of febrile neutropenia episodes, length to neutrophil count recovery, incidence and length of hospitalisation, number of infectious disease episodes, incidence and length of treatment delays, side effects (flu-like syndrome, bone pain and allergic reaction), relapse and overall mortality (death). SEARCH STRATEGY: The search covered the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CANCERLIT, LILACS, and SciElo. We manually searched records of conference proceedings of ASCO and ASH from 1985 to 2003 as well as databases of ongoing trials. We consulted experts and scanned references from the relevant articles. SELECTION CRITERIA: We looked for randomised controlled trials (RCTs) comparing CSF with placebo or no treatment as primary or secondary prophylaxis to prevent febrile neutropenia in children with ALL. DATA COLLECTION AND ANALYSIS: Two authors independently selected, critically appraised studies and extracted relevant data. The end points of interest were:* Primary end points: number of febrile neutropenia episodes and overall mortality (death) * Secondary end points: time to neutrophil count recovery, incidence and length of hospitalisation, number of infectious diseases episodes, incidence and length of treatment delays, side effects (flu-like syndrome, bone pain and allergic reaction) and relapse. We conducted a meta-analysis of these end points and expressed the results as Peto odds ratios. For continuous outcomes we calculated a weighted mean difference and a standardised mean difference. For count data, meta-analysis of the logarithms of the rate ratios using generic inverse variance was employed. MAIN RESULTS: We scanned more than 5500 citations and included six studies with a total of 332 participants in the analysis. There were insufficient data to assess the effect on survival. The use of CSF significantly reduced the number of episodes of febrile neutropenia episodes (Rate Ratio = 0.63; 95% confidence interval (CI) 0.46 to 0.85; p =0.003, with substantial heterogeneity), the length of hospitalisation (weighted mean difference (WMD) = -1.58; 95% CI -3.00 to -0.15; p = 0.03), and number of infectious diseases episodes (Rate Ratio=0.44; 95%CI 0.24 to 0.80; p=0.002). In spite of these results, CSF did not influence the length of episodes of neutropenia (WMD = -1.11; 95% CI -3.55 to 1.32; p = 0.4) or delays in chemotherapy courses (Rate Ratio=0.77; 95%CI 0.49 to 1,23; p=0.28) . AUTHORS' CONCLUSIONS: Children with ALL treated with CSF benefit from shorter hospitalisation and fewer infections. However, there was no evidence for a shortened duration of neutropenia nor fewer treatment delays, and no useful information about survival. The role of CSF regarding febrile neutropenia episodes is still uncertain. Although current data shows statistical benefit for CSF use, substantial heterogeneity between included trials does not allow this conclusion.

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BACKGROUND: Febrile neutropenia is a frequent event for cancer patients undergoing chemotherapy and it is potentially a life threatening situation. The current treatment is supportive care plus antibiotics. Colony stimulating factors (CSF) are cytokines that stimulate and accelerate the production of one or more cellular lines in bone marrow. Some clinical trials addressed the question of whether the addition of CSF to antibiotics (ATB) could improve the outcomes of patients with febrile neutropenia. The results of these trials are conflicting and no definitive conclusion could be reached. OBJECTIVES: To evaluate the safety and effectiveness of adding colony stimulating factors to ATB when treating febrile neutropenia caused by cancer chemotherapy. SEARCH STRATEGY: The search covered the major electronic databases: CANCERLIT, EMBASE, LILACS, MEDLINE, SCI and The Cochrane Controlled Trials Register. Experts were consulted and references from the relevant articles scanned. SELECTION CRITERIA: We looked for all randomized controlled trials (RCTs) that compare CSF plus antibiotics versus antibiotics alone for the treatment of established febrile neutropenia in adults and children. DATA COLLECTION AND ANALYSIS: Two of the reviewers independently selected, critically appraised and extracted data from the studies. A meta-analysis of the select studies was performed, using Review Manager. MAIN RESULTS: More than 8000 references were screened. Thirteen studies were included. The overall mortality was not influenced by the use of CSF [Odds Ratio (OR) = 0.68; 95% Confidence Interval (CI) = 0.43 to 1.08; p=0.1]. A marginally significant result was obtained for the use of CSF in reducing infection related mortality [OR= 0.51; 95% CI = 0.26 to 1.00; p=0.05], but this result was highly influenced by one study. When this study is excluded from our analysis, this possible benefit disappears [OR= 0.85; 95% CI = 0.33 to 2.20; p= 0.7]. The group of patients treated with CSF had a shorter length of hospitalization [Hazard Ratio (HR) = 0.63; 95% CI = 0.49 to 0.82; p=0.0006] and a shorter time to neutrophil recovery [HR= 0.32; 95% CI = 0.23 to 0.46; p < 0.00001]. REVIEWER'S CONCLUSIONS: The use of CSF in patients with febrile neutropenia due to cancer chemotherapy does not affect overall mortality, but reduces the amount of time spent in hospital and the neutrophil recovery period. It was not clear whether CSF has an effect on infection-related mortality.

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BACKGROUND: Low molecular weight heparins have been shown to be effective and safe for prevention of venous thromboembolism. There is accumulating evidence that these new anticoagulants are also effective and safe for treatment of venous thromboembolism. OBJECTIVES: The objective of this review was to determine the effect of fixed-dose, subcutaneous low molecular weight heparins compared with adjusted-dose, intravenous or subcutaneous, unfractionated heparin for initial treatment of acute deep venous thrombosis or pulmonary embolism. SEARCH STRATEGY: Trials were identified from the Cochrane Peripheral Vascular Diseases Group trials register and LILACS. The reviewers contacted colleagues and representatives of pharmaceutical companies for additional information about trials. SELECTION CRITERIA: Randomised trials comparing fixed-dose, subcutaneous low molecular weight heparin with adjusted-dose, intravenous or subcutaneous, unfractionated heparin in patients with venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trials for inclusion and quality, and extracted data independently. MAIN RESULTS: Fourteen studies with a total of 4754 patients were included. By the end of follow up in ten trials, thrombotic complications occurred in 86 (4.3%) of the 1998 patients treated with low molecular weight heparin, compared with 113 (5.6%) of the 2021 patients treated with unfractionated heparin (odds ratio 0.76, 95% confidence interval 0.57 to 1.01). In eight trials a reduction in thrombus size was shown by 60% treated with low molecular weight heparin and 54% treated with unfractionated heparin (odds ratio 0.77, 95% confidence interval 0.61 to 0.97). At the end of the initial treatment period, in all 14 of the trials, major haemorrhages occurred in 30 (1.3%) of the 2353 patients treated with low molecular weight heparin, compared with 51 (2.1%) of the 2401 patients treated with unfractionated heparin (odds ratio 0.60, 95% confidence interval 0.39 to 0.93). By the end of follow up in 11 trials, 135 (6.4%) of the 2108 patients treated with low molecular weight heparin had died, compared with 172 (8.0%) of the 2137 patients treated with unfractionated heparin (odds ratio 0.78, 95% confidence interval 0.62 to 0.99). Five studies with a total of 1636 patients examined proximal (above the knee) thrombosis; 814 treated with low molecular weight heparin and 822 with unfractionated heparin. A sub-analysis of these trials showed statistically significant reductions favouring the action of low molecular weight heparin in three areas: thrombotic complications; major haemorrhages; and overall mortality. By the end of follow up 39 (4. 8%) patients treated with low molecular weight heparin had thrombotic complications, compared with 64 (7.8%) treated with unfractionated heparin (odds ratio 0.60, 95% confidence interval 0. 40 to 0.89). Major haemorrhages occurred in 8 (1.0%) treated with low molecular weight heparin, compared with 68 (8.3%) treated with unfractionated heparin (odds ratio 0.44, 95% confidence interval 0. 21 to 0.95). By the end of follow up, 44 (5.4%) treated with low molecular weight heparin had died, compared with 68 (8.3%) treated with unfractionated heparin (odds ratio 0.64, 95% confidence interval 0.43 to 0.93). REVIEWER'S CONCLUSIONS: Low molecular weight heparin is at least as effective as unfractionated heparin in preventing recurrent venous thromboembolism, and significantly reduces the occurrence of major haemorrhage during initial treatment and overall mortality at the end of follow-up. It can be adopted safely as the standard therapy for deep venous thrombosis, and studies comparing individual low molecular weight heparins are merited.

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OBJECTIVE: To define and disseminate the optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature (LILACS). This strategy was elaborated based on the optimal search strategy for MEDLINE recommended by Cochrane Collaboration for the identification of clinical trials in electronic databases. DESIGN: Technical information. SETTING: Clinical Trials and Meta-Analysis Unit, Federal University of São Paulo, in conjunction with the Brazilian Cochrane Center, São Paulo, Brazil. (http://www.epm.br/cochrane). DATA: LILACS/CD-ROM (Latin American and Caribbean Health Science Information Database), 27th edition, January 1997, edited by BIREME (Latin American and Caribbean Health Science Information Center). LILACS Indexes 670 journals in the region, with abstracts in English, Portuguese or Spanish; only 41 overlap in the MEDLINE-EMBASE. Of the 168,902 citations since 1982, 104,016 are in human trials, and 38,261 citations are potentiality clinical trials. Search strategy was elaborated combining headings with text word in three languages, adapting the interface of the LILACS. We will be working by locating clinical trials in LILACS for Cochrane Controlled Trials Database. This effort is being coordinated by the Brazilian Cochrane Center.

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