100% peer review in radiation oncology: is it feasible?

PURPOSE: Peer review has been proposed as a strategy to ensure patient safety and plan quality in radiation oncology. Despite its potential benefits, barriers commonly exist to its optimal implementation in daily clinical routine. Our purpose is to analyze peer-review process at our institution. METHODS AND MATERIALS: Based on our group peer-review process, we quantified the rate of plan changes, time and resources needed for this process. Prospectively, data on cases presented at our institutional peer-review conference attended by physicians, resident physicians and physicists were collected. Items such as time to present per case, type of patient (adult or pediatric), treatment intent, dose, aimed technique, disease location and receipt of previous radiation were gathered. Cases were then analyzed to determine the rate of major change, minor change and plan rejection after presentation as well as the median time per session. RESULTS: Over a period of 4 weeks, 148 cases were reviewed. Median of attendants was six physicians, three in-training-physicians and one physicist. Median time per session was 38 (4-72) minutes. 59.5% of cases presented in 1-4 min, 32.4% in 5-9 min and 8.1% in ≥ 10 min. 79.1% of cases were accepted without changes, 11.5% with minor changes, 6% with major changes and 3.4% were rejected with indication of new presentation. Most frequent reason of change was contouring corrections (53.8%) followed by dose or fractionation (26.9%). CONCLUSION: Everyday group consensus peer review is an efficient manner to recollect clinical and technical data of cases presented to ensure quality radiation care before initiation of treatment as well as ensuring department quality in a feedback team environment. This model is feasible within the normal operation of every radiation oncology Department.

Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population.

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.

In silico identification of conserved intercoding sequences in Leishmania genomes: unraveling putative cis-regulatory elements.

In silico analyses of Leishmania spp. genome data are a powerful resource to improve the understanding of these pathogens' biology. Trypanosomatids such as Leishmania spp. have their protein-coding genes grouped in long polycistronic units of functionally unrelated genes. The control of gene expression happens by a variety of posttranscriptional mechanisms. The high degree of synteny among Leishmania species is accompanied by highly conserved coding sequences (CDS) and poorly conserved intercoding untranslated sequences. To identify the elements involved in the control of gene expression, we conducted an in silico investigation to find conserved intercoding sequences (CICS) in the genomes of L. major, L. infantum, and L. braziliensis. We used a combination of computational tools, such as Linux-Shell, PERL and R languages, BLAST, MSPcrunch, SSAKE, and Pred-A-Term algorithms to construct a pipeline which was able to: (i) search for conservation in target-regions, (ii) eliminate CICS redundancy and mask repeat elements, (iii) predict the mRNA's extremities, (iv) analyze the distribution of orthologous genes within the generated LeishCICS-clusters, (v) assign GO terms to the LeishCICS-clusters, and (vi) provide statistical support for the gene-enrichment annotation. We associated the LeishCICS-cluster data, generated at the end of the pipeline, with the expression profile of L. donovani genes during promastigote-amastigote differentiation, as previously evaluated by others (GEO accession: GSE21936). A Pearson's correlation coefficient greater than 0.5 was observed for 730 LeishCICS-clusters containing from 2 to 17 genes. The designed computational pipeline is a useful tool and its application identified potential regulatory cis elements and putative regulons in Leishmania.

Characterization of bovine transcripts preferentially expressed in testis and with a putative role in spermatogenesis.

Although the number of genes known to be associated with bovine spermatogenesis has increased in the past few years, regulation of this biological process remains poorly understood. Therefore, discovery of new male fertility genetic markers is of great value for assisted selection in commercially important cattle breeds, e.g., Nelore, that have delayed reproductive maturation and low fertility rates. The objective of the present study was to identify sequences associated with spermatogenesis that could be used as fertility markers. With RT-PCR, the following five transcripts preferentially expressed in adult testis were detected: TET(656) detected only in adult testis; TET(868) and TET(515) expressed preferentially in adult testis but also detected in fetal gonads of both sexes; and TET(456) and TET(262,) expressed primarily in the testis, but also present in very low amounts in somatic tissues. Based on their homologies and expression profiles, we inferred that they had putative roles in spermatogenesis. Detection of sequences differentially expressed in testis, ovary, or both, was a useful approach for identifying new genes related to bovine spermatogenesis. The data reported here contributed to discovery of gene pathways involved in bovine spermatogenesis, with potential for prediction of fertility.

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico.

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristics of two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restricted fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype (P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristicsof two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restrited fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype(P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

46,XX sex reversal.

In humans, sexual differentiation is directed by SRY, a master regulatory gene located at the Y chromosome. This gene initiates the male pathway or represses the female pathway by regulating the transcription of downstream genes; however, the precise mechanisms by which SRY acts are largely unknown. Moreover, several genes have recently been implicated in the development of the bipotential gonad even before SRY is expressed. In some individuals, the normal process of sexual differentiation is altered and a sex reversal disorder is observed. These subjects present the chromosomes of one sex but the physical attributes of the other. Over the past years, considerable progress has been achieved in the molecular characterization of these disorders by using a combination of strategies including cell biology, animal models, and by studying patients with these pathologic entities.

Characterisation of three chromosomal ends of Leishmania major reveals transcriptional activity across arrays of reiterated and unique sequences.

The 36 chromosomes of the parasite Leishmania major range in size from 200 kb to approximately 2.5 Mb and variation between homologues seems to be restricted to the telomeric and subtelomeric regions. We have isolated three cosmids carrying the telomere hexameric repeat and assigned them to the extreme location of chromosomes 3, 7 and 20. When considering the distribution of repetitive sequences, Southern analysis of the three chromosomal ends indicated the existence of at least two classes of chromosomal extremities: one of them is composed almost exclusively of unique sequences and the other is characterised by patches of both reiterated and unique sequences. We devised a transfection-based strategy that allowed the determination of a map of transcripts in each of the regions examined. Sequencing of the chromosome 20 cosmid revealed the existence of a novel class of reiterated sequence, LST-R378, and 10 ORFs drawing a map of putative genes compatible with the map of transcripts.

Reduced bone mineral density at diagnosis and bone mineral recovery during treatment in children with Graves' disease.

OBJECTIVES: In children with Graves' disease, the prevalence of osteopenia is unknown, and the possible restoration of bone mass by antithyroid treatment has not been evaluated. The aim of this study was to prospectively evaluate the bone mineral density (BMD) and bone metabolism at diagnosis and after 1 and 2 years of medical treatment. Twenty-six children (19 girls and 7 boys) aged 11 +/- 3.4 years (range 3.4 to 15.3 years) were studied. STUDY DESIGN: BMD of the lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry. Values were compared with those of healthy children of similar age, sex, and pubertal stage. RESULTS: At diagnosis the mean BMD (standard deviation score [SDS]) was significantly reduced in both sites (P <.001) with a preferential loss of cortical bone (femoral BMD = -1.7 +/- 1.0 SDS) rather than trabecular bone (lumbar spine BMD = -0.8 +/- 1.1 SDS) (P =.003). Severe osteopenia (below -2 SDS) was found in 11 (42%) of 26 patients. Osteocalcin was significantly higher than in the control group (P <.0001), but other bone metabolism markers were normal. During treatment (n = 19) a significant gain in femoral (F = 14.7; P =.001) and lumbar spine (F = 5; P =.02) BMD (SDS) was observed, and none of the patients showed osteopenia. The annual percent change in the BMD values at the femoral (+23% +/- 11% and +6% +/- 4%, respectively, during the first and second years) and lumbar spine (+19% +/- 9% and +6% +/- 5%, respectively, during the first and second years) sites was greater during the first year than during the second year of treatment (P <.02 for femoral, P <.04 for lumbar spine). No significant age difference in BMD SD score or in BMD percent change values was observed. Osteocalcin returned rapidly to normal values, and all other bone metabolism markers remained in the normal range. CONCLUSIONS: In conclusion, severe osteopenia was observed at diagnosis in children with Graves' disease but was rapidly corrected after 1 and 2 years of treatment. Initial reduced bone mass with high bone turnover caused by hyperthyroidism was corrected after 1 year of euthyroid conditions.

Spontaneous hepatocellular carcinoma in Saimiri boliviensis.

Hepatocellular carcinomas are rare in nonhuman primates. In this study we found the first naturally occurring hepatocellular carcinoma in a Squirrel Monkey (Saimiri boliviensis) of at least 24 years of age. In the necropsy, the liver was cirrhotic and contained multiple tumorous nodules, which varied in diameter from 3 to 15 mm. The lungs also contained small neoplastic masses. In the histological study, samples of liver, lungs, and other organs were taken and fixed in 10% buffered formalin, embedded in paraffin, cut at 5 microns, and colored with hematoxylin and eosin. The histological study of the liver permitted the detection of multiple masses of neoplastic liver cells in a closely packed trabecular configuration surrounded by a well-developed capillary basement membrane. Cirrhotic changes also were observed in the liver. The histological study of the lung confirmed the metastasis of the hepatocellular carcinoma. Metastasis was not found in other organs.

[Analysis of 1,000 hysterectomies. Technical simplifications and reflections. ISSSTE hospitals]. / Análisis de 1,000 histerectomías. Simplificaciones técnicas y reflexiones. Hospitales del ISSSTE.

1,000 hysterectomies are reported by the author in a space of 20 years in four hospitals of ISSSTE. Some clinic-pathological parameters were analyzed, morbi-mortality, etc. The obtained results are informed using a simplification on the surgical techniques. The most frequent symptoms were menstrual disorders, and the most frequent diagnosis was myomatosis with (61.2%) average age between 35-45 years old. All were total hysterectomies, intrafascial 92.6% and abdominal 74.8%. Attention is called upon the fact that 7.2% of the patients presented pelvic congestion post tubaric occlusion and the association of adenomyosis. The overall morbidity was 12.2% being urosepsis the most frequent. Mortality was in one case of giant interligamentary myoma and DIC. Blood transfusion was needed just in 4.2%. We think that the surgical simplification here announced offer more safety, less morbidity, less bleeding and brief surgical time. More over, a critical analysis was made about use and abuse of this kind of surgical intervention.