Skin Coverage of the Middle-Distal Segment of the Leg With a Pedicled Perforator Flap

Objective: This is a clinical study of our experience using pedicle perforator flaps to cover skin defects in the middle and distal segment of the leg. Design: Prospective study. Setting: University hospital. Patients/Intervention: Twenty-four patients underwent treatment of a skin defect in the middle or distal segment of the leg by means of pedicled flaps based on perforating arteries. The perforating arteries were located before the operation by means of echo-Doppler examination. The flaps were planned in propeller fashion (21 cases) and as advancement (three cases). Main Outcome Measurements: The results were evaluated according the origin of perforator flap, size of the flap, and donor area and viability of the flap. The success rate of the echo-Doppler to identify the location of perforator vessel was also evaluated. Results: In nine cases, the perforating vessels originated from the fibular artery, in 10 the posterior tibial artery, and in five the anterior tibial artery. The mean size of the flaps was 5 cm in width by 12 cm in length. The success rate using an echo-Doppler was 87%. The flaps were fully viable in 20 cases and partially viable in four cases. Conclusion: On the basis of these results, it is concluded that perforating flaps are a good choice of treatment for skin losses, especially in the distal segment of the leg, and could be an alternative option for the use of free microsurgical flaps.

Associations of serious mental illness with earnings: results from the WHO World Mental Health surveys

Background Burden-of-illness data, which are often used in setting healthcare policy-spending priorities, are unavailable for mental disorders in most countries. Aims To examine one central aspect of illness burden, the association of serious mental illness with earnings, in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Method The WMH Surveys were carried out in 10 high-income and 9 low- and middle-income countries. The associations of personal earnings with serious mental illness were estimated. Results Respondents with serious mental illness earned on average a third less than median earnings, with no significant between-country differences (chi(2)(9)=5.5-8.1, P=0.5-0.79). These losses are equivalent to 0.3-0.8% of total national earnings. Reduced earnings among those with earnings and the increased probability of not earning are both important components of these associations: Conclusions These results add to a growing body of evidence that mental disorders have high societal costs. Decisions about healthcare resource allocation should take these costs into consideration.

Molecular cloning and characterization of a ripening-induced polygalacturonase related to papaya fruit softening

Pulp softening is one of the most remarkable changes during ripening of papaya (Carica papaya) fruit and it is a major cause for post-harvest losses. Although cell wall catabolism has a major influence on papaya fruit, quality information on the gene products involved in this process is limited. A full-length polygalacturonase cDNA (cpPG) was isolated from papaya pulp and used to study gene expression and enzyme activity during normal and ethylene-induced ripening and after exposure of the fruit to 1-MCP. Northern-blot analysis demonstrated that cpPG transcription was strongly induced during ripening and was highly ethylene-dependent. The accumulation of cpPG transcript was paralleled by enzyme activity, and inversely correlated to the pulp firmness. Preliminary in silica analysis of the cpPG genomic sequence revealed the occurrence of putative regulatory motifs in the promoter region that may help to explain the effects of plant hormones and non-abiotic stresses on papaya fruit firmness. This newly isolated cpPG is an important candidate for functional characterization and manipulation to control the process of pulp softening during papaya ripening. (C) 2009 Elsevier Masson SAS. All rights reserved.

Cost-Effectiveness of Palliation of Unresectable Esophageal Cancer

Introduction Different modalities of palliation for obstructive symptoms in patients with unresectable esophageal cancer (EC) exist. However, these therapeutic alternatives have significant differences in costs and effectiveness. Methods A Markov model was designed to compare the cost-effectiveness (CE) of self-expandable stent (SES), brachytherapy and laser in the palliation of unresectable EC. Patients were assigned to one of the strategies, and the improvement in swallowing function was compared given the treatment efficacy, probability of survival, and risks of complications associated to each strategy. Probabilities and parameters for distribution were based on a 9-month time frame. Results Under the base-case scenario, laser has the lowest CE ratio, followed by brachytherapy at an incremental cost-effectiveness ratio (ICER) of $4,400.00, and SES is a dominated strategy. In the probabilistic analysis, laser is the strategy with the highest probability of cost-effectiveness for willingness to pay (WTP) values lower than $3,201 and brachytherapy for all WTP yielding a positive net health benefit (NHB) (threshold $4,440). The highest probability of cost-effectiveness for brachytherapy is 96%, and consequently, selection of suboptimal strategies can lead to opportunity losses for the US health system, ranging from US$ 4.32 to US$ 38.09 million dollars over the next 5-20 years. Conclusion Conditional to the WTP and current US Medicare costs, palliation of unresectable esophageal cancers with brachytherapy provides the largest amount of NHB and is the strategy with the highest probability of CE. However, some level of uncertainly remains, and wrong decisions will be made until further knowledge is acquired.

Can an adequate energy intake be able to reverse the negative nitrogen balance in mechanically ventilated critically ill patients?

Purpose: Adequate energy provision and nitrogen losses prevention of critically ill patients are essentials for treatment and recovery. The aims of this study were to evaluate energy expenditure (EE) and nitrogen balance (NB) of critically ill patients, to classify adequacy of energy intake (El), and to verify adequacy of El capacity to reverse the negative NB. Methods: Seventeen patients from an intensive care unit were evaluated within a 24-hour period. Indirect calorimetry was performed to calculate patient`s EE and Kjeldhal for urinary nitrogen analysis. The total El and protein intake were calculated from the standard parenteral and enteral nutrition infused. Underfeeding was characterized as El 90% or less and overfeeding as 110% or greater of EE. The adequacy of the El (El EE(-1) x 100) and the NB were estimated and associated with each other by Spearman coefficient. Results: The mean EE was 1515 +/- 268 kcal d(-1) and most of the patients (11/14) presented a negative NB (-8.2 +/- 4.7 g.d(-1)). A high rate (53%) of inadequate energy intake was found, and a positive correlation between El EE(-1) and NB was observed (r = 0.670; P = .007). Conclusion: The results show a high rate of inadequate El and negative NB, and equilibrium between El and EE may improve NB. Indirect calorimetry can be used to adjust the energy requirements in the critically ill patients. (C) 2010 Elsevier Inc. All rights reserved.

Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa

Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid plexus papillomas, have been rarely described. In the present report, the cytogenetic investigation of an atypical choroid plexus papilloma occurring at the posterior fossa of a 16-year-old male is described. Comparative genome hybridization analysis demonstrated gains of genetic material from almost all chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and loss of chromosome Y. The presence of polyploid cells was confirmed by fluorescence in situ hybridization analysis with probes directed to centromeric regions. Furthermore, the microscopic analysis of cultures showed nuclear buds, nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the presence of complex chromosomal abnormalities. Previous cytogenetic studies on choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid karyotypes. To the best of our knowledge, this is the first report of polyploidy in choroid plexus papilloma of intermediate malignancy grade. Although the mechanisms beneath such genome duplication remain to be elucidated, the observed abnormal nuclear shapes indicate constant restructuring of the tumor`s genome and deserves further investigation.

Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas

The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas. (C) 2010 Elsevier Inc. All rights reserved.

Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity

Identification of the 1p/19q allelic status in gliomas, primarily those with a major oligodendroglial component, has become an excellent molecular complement to tumor histology in order to identify those cases sensitive to chemotherapy. In addition to loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA) has been shown to be an alternative methodology to identify deletions of those chromosome arms. We used MLPA to explore the 1p and 19q glioblastomas, and a series of 76 gliomas: 41 tumors with a major oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We compared the MLPA findings of the oligodendroglial cases with those previously obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas displayed identical findings by both LOH and MLPA, and losses at either 1p and/or 19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree with data previously reported comparing MLPA versus FISH or CGH in gliomas and suggest that MLPA can be used in the identification 1p/19q allelic deletions on these brain neoplams. (c) 2009 Elsevier Inc. All rights reserved. reserved.

Identification of genetic alterations by multiple ligation-dependent probe amplification (MLPA) analysis in oligodendrogliomas

Concurrent deletion at 1p/19q is a common signature of oligodendrogliomas, and it may, be identified in low-grade tumours (grade II) suggesting it represents an early event in the development of these brain neoplasms. Additional non-random changes primarily involve CDKN2A, PTEN and EGFR. Identification of all of these genetic changes has become an additional parameter in the evaluation of the clinical patients` prognosis, including good response to conventional chemotherapy. Multiple ligation-dependent probe amplification (MLPA) analysis is a new methodology that allows an easy identification of the oligodendrogliomas` abnormalities in a single step. No need of the respective constitutional DNA from each patient is another advantage of this method. We used MLPA kits P088 and P105 to determine the molecular characteristics of a series of 40 oligodendrogliomas. Deletions at I p and 19q were identified in 45% and 65% of cases, respectively. Alterations of EGFR, CDKN2A, ERBB2, PTEN and TP53 were also identified in variable frequencies among 7% to 35% of tumours. These findings demonstrate that MLPA is a reliable technique to the detection of molecular genetic changes in oligodendrogliomas.

Meningiomas and schwannomas: Molecular subgroup classification found by expression arrays

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

New recurrent deletions in the PPAR gamma and TP53 genes are associated with childhood myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a rare hematological malignancy in children. It was performed FISH analysis in 19 pediatric MDS patients to investigate deletions involving the PPAR gamma and TP53 genes. Significant losses in the PPAR gamma gene and deletions in the tumor suppressor gene TP53 were observed in 17 and 18 cases, respectively. Using quantitative RT-PCR, it was detected PPAR gamma transcript downexpression in a subset of these cases. G-banding analysis revealed 17p deletions in a small number of these cases. One MDS therapy-related patient had neither a loss of PPAR gamma nor TP53. These data suggest that the PPAR gamma and TP53 genes may be candidates for molecular markers in pediatric MDS, and that these potentially recurrent deletions could contribute to the identification of therapeutic approaches in primary pediatric MDS. (C) 2008 Elsevier Ltd. All fights reserved.

Development and agronomic performance of common bean lines simultaneously resistant to anthracnose, angular leaf spot and rust

The common bean is affected by several pathogens that can cause severe yield losses. Here we report the introgression of resistance genes to anthracnose, angular leaf spot and rust in the `carioca-type` bean cultivar `Ruda`. Initially, four backcross (BC) lines were obtained using `TO`, `AB 136`, `Ouro Negro` and `AND 277` as donor parents. Molecular fingerprinting was used to select the lines genetically closer to the recurrent parent. The relative genetic distances between `Ruda` and the BC lines varied between 0.0% and 1.99%. The BC lines were intercrossed and molecular markers linked to the resistance genes were used to identify the plants containing the genes of interest. These plants were selfed to obtain the F(2), F(3) and F(4) plants which were selected based on the presence of the molecular markers mentioned and resistance was confirmed in the F(4) generation by inoculation. Four F(4:7) pyramid lines with all the resistance genes showed resistance spectra equivalent to those of their respective donor parents. Yield tests showed that these lines are as productive as the best `carioca-type` cultivars.

Loss of samples in the tissue microarray technique: comparison between slides using adhesive tape and silanized slides

The tissue microarray (TMA) technique allows multiple tissue samples in a single block. Commercial adhesive tape is used to avoid the loss of tissue samples during the immunostaining process. Few reports exist in the literature comparing the use of these adhesive tapes to other adhesive techniques. The objective of this study was to compare loss of sections adhered to slides using commercial adhesive tapes versus using silanized only slides. TMA was constructed with varying tissues using a fixed-base device (Beecher Instruments), placing 108 cylinders of 1 mm diameter in duplicate, spaced 1.2 mm apart. Section of 4 mu m were cut from the TMA block and adhered to 30 silanized slides and 30 commercial glass slides using adhesive tape, according to manufacturer`s recommendations. Vimentin immunoexpression was evaluated by immunohistochemistry. Antigenic recovery was realized in citrate buffer using a microwave oven. Cylinder loss in the immunohistochemical process was quantified and expressed as: total (>80%), almost complete (75-79%), or partial (50-74%). The commercial adhesive tape group presented lesser total loss (1.1 versus 6.4%), almost complete loss (2.2 versus 3.5%), and partial loss (2.1 versus 3.8%) than the silanized slide group (ANOVA, P < 0.05). The sum of total and almost complete losses in the silanized slide group was 9.9%, greater than the losses in slides using commercial adhesive tapes (3.3%) and less than reported and considered acceptable in the literature (10-30%). In conclusion, the use of silanized only slides presents very satisfactory results, requires less training, and reduces costs significantly, thus justifying their use in research.

A study of adrenocortical tumors in children and adolescents by a comparative genomic hybridization technique

Adrenocortical tumors (ACT) are rare neoplasms of the adrenal glands accounting for 0.2% of all pediatric cancers. However, the incidence of ACT in South Brazilian children is 10 to 15 times greater than the worldwide incidence. Comparative genomic hybridization studies have revealed the presence of a high degree of chromosomal instability in ACT. We evaluated 16 ACT, 8 of them carcinomas and 8 adenomas. The presence of changes in DNA copy numbers was determined by comparative genomic hybridization, and the findings were validated by real-time polymerase chain reaction on the basis of IGF-II gene expression. The adenomas showed a mean of 19.7 imbalances per case, with the most frequent gain and loss being 4p15.1-p15.3 and 20p11.2-p13.2, respectively. The carcinomas presented with a mean of 35.5 imbalances per case, with the more frequent gain being 2q14.1-q24.3 and the more frequent losses being 3q21-q26.2, 20q12-qter, and 22q11.2-q13.3. The most frequent imbalances in both adenomas and carcinomas were gains of 1p21-p31.2, 2p12-p21 and loss of 20p11.2-p12. The expression of IGF-II mRNA (11p15.5) was higher in samples that presented with a gain of this region. It has been established that great genomic instability exists in pediatric ACT.

Intestinal bacterial overgrowth after Roux-en-Y gastric bypass

The aim of the present study was to report the occurrence of serious subnutrition, associated to intestinal bacterial overgrowth, in two patients submitted to bariatric surgery. Two female patients (body mass index, 49 and 50 kg/m(2), respectively) were submitted to Y-en-Roux gastric bypass. The first patient evolved a 52% loss of body weight within 21 months after surgery; the other, a 34% loss of initial body weight within 15 months after surgery, results corresponding, respectively, to 62 and 45 kg weight losses. However, both patients reported asthenia, hair fallout, and edema, and one also reported diarrhea, but none was feverish. Their respective albuminemias were of 24 and 23 g/l. A respiratory hydrogen test suggested bacterial hyperproliferation. Thirty days after ciprofloxacin and tetracyclin treatments, they showed improved albumin levels and nutritional states, both confirmed by results of hydrogen breath tests. Bacterial overgrowth is an important complication that can compromise clinical evolution of patients submitted to intestinal surgery like gastroplasty with Y-Roux anastomosis. In cases of clinical suspicion or a confirmed diagnosis, adequate antibiotics, sometimes requiring to be cyclically repeated, should be administered.