A treatment planning comparison of photon stereotactic ablative radiotherapy and proton beam therapy for the re-irradiation of pelvic cancer recurrence.

BACKGROUND: Patients who experience a pelvic cancer recurrence in or near a region that received initial radiotherapy, typically have few options for treatment. Organs at risk (OAR) have often reached their dose constraint limits leaving minimal dose remaining for standard re-irradiation (reRT). However, photon based stereotactic ablative radiotherapy (SABR) has been utilised for reRT with promising initial results although meeting OAR constraints can be challenging. Proton beam therapy (PBT) could offer an advantage. MATERIALS AND METHODS: SABR plans used for treatment for ten pelvic reRT patients were dosimetrically compared to PBT plans retrospectively planned using the same CT and contour data. PBT plans were created to match the CTV dose coverage of SABR treatment plans with V100% ≥95%. An 'as low as reasonably achievable' approach was taken to OAR tolerances with consideration of OAR dose from the initial radiation (using equivalent dose in 2 Gy fractions). RESULTS: Dosimetric comparison of relevant OAR statistics showed a decrease in OAR dose using PBT over SABR in all patients, with equivalent target coverage. The largest statistically significant reduction was seen for the colon D0.5 cm3 with a median reduction from 13.1 Gy to 5.9 Gy. There were statistically significant dose reductions in the median dose to small bowel, sacral plexus and cauda equina. CONCLUSION: PBT has the potential for significant dose reductions for OARs in the pelvic reRT setting compared to SABR. However, it remains unclear if the magnitude of these OAR dose reductions will translate into clinical benefit.

Three decades of occupational individual monitoring at the University of São Paulo.

As the ionizing radiation to which workers are exposed is related to possible harmful biological effect, its dose evaluation gains relevance. Although the effects of low doses are still controversial, the radiation protection authorities assume that any dose of ionizing radiation is potentially harmful to the human health and adopt the linear non-threshold model for the dose-effect relation. The Dosimetry Laboratory of the Institute of Physics of the University of São Paulo performs the external individual monitoring of workers exposed to X- and gamma-rays since 1981, with the technique of thermoluminescence. Currently, ~500 badges are provided to the university professionals mostly working in research laboratories and hospitals. Data of individual annual dose equivalent collected from 1995 to 2015 and the performance of the monitoring service are presented in this paper.

The patient with recurrent oral ulceration.

This paper discusses the range of recurrent oral ulceration which affects the oral mucosa. Types of ulceration covered in this paper include traumatic, infective, aphthous, ulceration related to the oral dermatoses, drug-induced, ulceration as a manifestation of systemic disease and ulceration indicating malignancy. Aspects of the aetiology, diagnosis and management of common oral recurrent ulcerative conditions are reviewed from a clinical perspective as an aid to practising dentists.

Genomic duplication in Dyggve Melchior Clausen syndrome, a novel mutation mechanism in an autosomal recessive disorder.

BACKGROUND: Dyggve Melchior Clausen syndrome (DMC) is a severe autosomal recessive skeletal dysplasia associated with mental retardation. Direct sequencing of genomic DNA has identified causative mutations in the gene Dymeclin (chromosome 18q12-21), with the majority predicting the generation of a truncated protein product. OBJECTIVE: To carry out molecular genetic studies in three DMC kindreds. RESULTS: Two novel nonsense mutations and two complex genomic duplication events resulting in exon repetition were identified. CONCLUSIONS: Exon dosage assessment or mRNA analysis, in addition to direct genomic DNA sequencing, should be employed in the investigation of DMC affected individuals. Genomic duplication may be the causative mutation mechanism in other autosomal recessive disorders.

A Full-Color Electroluminescent Device and Patterned Photoalignment Using Light-Emitting Liquid Crystals.

Blue, green, and red polymerizable light-emitting liquid crystals have been patterned photolithographically in a full-color liquid-crystal electroluminescent display. A new hole-transporting photoalignment copolymer is also reported and the spatial patterning of the polarization direction of emission is demonstrated.

Clinico-pathological conference 2002.

INTRODUCTION: Six cases are reported, each presented at the 11th Biennial Congress of the International Association of Oral Pathologists as an instructive case for differential diagnosis on the basis of clinical, imaging or histological features. CLINICAL PICTURE: Case diagnoses included a large, possibly intraosseous, myofibroma presenting with an oral mass; Langerhans cell histiocytosis with facial skin lesions; an intraosseous vascular hamartoma of the maxilla with worrying radiological features; an unusual mixed radiolucency of the jaw caused by cemento-ossifying fibroma; an osteosarcoma of the posterior mandible causing a well-defined radiolucency and an intraoral squamous cell carcinoma in a child.

Relationship of phenotype and genotype in X-linked amelogenesis imperfecta.

X-linked amelogenesis imperfectas (AI) resulting from mutations in the amelogenin gene (AMELX) are phenotypically and genetically diverse. Amelogenin is the predominant matrix protein in developing enamel and is essential for normal enamel formation. To date, 12 allelic AMELX mutations have been described that purportedly result in markedly different expressed amelogenin protein products. We hypothesize that these AMELX gene mutations result in unique and functionally altered amelogenin proteins that are associated with distinct amelogenesis imperfecta phenotypes. The AMELX mutations and associated phenotypes fall generally into three categories. (1) Mutations (e.g., signal peptide mutations) causing a total of loss of amelogenin protein are associated with a primarily hypoplastic phenotype (though mineralization defects also can occur). (2) Missense mutations affecting the N-terminal region, especially those causing changes in the putative lectin-binding domain and TRAP (tyrosine rich amelogenin protein) region of the amelogenin molecule, result in a predominantly hypomineralization/hypomaturation AI phenotype with enamel that is discolored and has retained amelogenin. (3) Mutations causing loss of the amelogenin C terminus result in a phenotype characterized by hypoplasia. The consistent association of similar hypoplastic or hypomineralization/hypomaturation AI phenotypes with specific AMELX mutations may help identify distinct functional domains of the amelogenin molecule. The phenotype-genotype correlations in this study suggest there are important functional domains of the amelogenin molecule that are critical for the development of normal enamel structure, composition, and thickness.

Unusual manifestations in X-linked amelogenesis imperfecta.

This paper describes a female with X-linked amelogenesis imperfecta (XAI). This case is unusual in having taurodontism, pulpal calcifications, coronal defects prior to tooth eruption and unerupted teeth. These findings have been reported in some cases of autosomal dominant and autosomal recessive AI but have not previously been documented in XAI.

It's only teeth - are there limits to genetic testing?

Dental genetic disorders can cause severe social and psychological effects in affected individuals. The cost of treatment can be considerable, not only in financial terms but also in time spent during treatment. In theory it is, or will soon be, possible to use advances in molecular genetics for pre-natal testing, for selection of embryos using in vitro fertilization techniques, and for gene therapy. The questions we pose are whether these approaches are appropriate. We hope that this review will stimulate debate on these issues.

Amelogenesis imperfecta: a classification and catalogue for the 21st century.

Amelogenesis imperfecta (AI) is a collective term for a number of conditions with abnormal enamel formation. Many cases are inherited, either as an X-linked, autosomal dominant or autosomal recessive trait. Several classifications have evolved since 1945, based primarily on phenotype with the mode of inheritance being used in some systems as a secondary factor in allocating a case into a particular category. The benefits and shortcomings of these systems are reviewed. As we move into an era of establishing the molecular basis of AI we propose a robust mechanism for classification and cataloguing of the disorder which parallels systems used in medical genetics. This system is applicable to individuals and families irrespective of current or future knowledge of the molecular defect involved. We argue that this system is of more benefit to these individuals and families than previous classifications.

Juvenile mandibular chronic osteomyelitis: a distinct clinical entity.

Sclerosing osteomyelitis of the mandible is an uncommon disease of unknown aetiology. A series of eight female children (6 to 12 years old) with a distinct mandibular inflammatory disease were studied. Each presented with pain and a recurrent soft tissue swelling overlying a predominantly unilateral mandibular enlargement. On imaging, this deformity demonstrated a mixture of patchy sclerosis and radiolucency. A raised erythrocyte sedimentation rate was the only consistent serological finding. Treatment varied from symptomatic control with non-steroidal anti-inflammatory medication, to surgical management that included decortication and contouring and, in one case, resection with reconstruction. A potential protocol for treatment of this disease is given. The early age of onset of the disease process and the uniformity of the features distinguish this condition from other groups of disorders that, previously, have been collectively designated as chronic diffuse sclerosing osteomyelitis. It is proposed that this inflammatory disease of mandibular bone, in the paediatric patient, should be regarded as a separate clinical entity: 'juvenile mandibular chronic osteomyelitis'.

Molecular analysis for genetic counselling in amelogenesis imperfecta.

OBJECTIVE: To use molecular genetics to establish the mode of inheritance in a family with amelogenesis imperfecta. MATERIALS AND METHODS: The polymerase chain reaction was used to amplify exons of the amelogenin gene on the short arm of the X chromosome. RESULTS: A single base deletion mutation in exon 6 of the amelogenin gene was identified. This mutation was a single base deletion of a cytosine residue - 431delC - in codon 96 of exon 6, introducing a stop codon 30 codons downstream of the mutation in codon 126 of the exon. CONCLUSION: The firm establishment of an X-linked mode of inheritance affects the genetic counselling for this family.

Clinical and radiographic features of a family with autosomal dominant amelogenesis imperfecta with taurodontism.

This paper describes the clinical features of a family of four generations with autosomal dominant amelogenesis imperfecta with taurodontism (ADAIT). Considerable variation in phenotype was seen, both between individuals and within the dentition of some individuals. Many of the adults had received extensive dental restorative work. These findings re-enforce previous observations of variable phenotype in this and other forms of the condition and add to the argument for a revision of methods of classification. This history of this large family draws further attention to the restorative demands of this group of dental anomalies and, by their generous co-operation, will prove an invaluable help in the investigation by molecular genetic techniques of this disfiguring condition.

Amelogenesis imperfecta phenotype-genotype correlations with two amelogenin gene mutations.

Amelogenin, the predominant matrix protein in developing dental enamel, is considered essential for normal enamel formation, but its exact functions are undefined. Mutations in the AMELX gene that encodes for amelogenin protein cause X-linked amelogenesis imperfecta (AI), with phenotypes characterized by hypoplastic and/or poorly mineralized enamel. Eight different AMELX deletion and substitution mutations have been reported to date. The purpose here was to evaluate the genotype and phenotype of two large kindreds segregating for X-linked AI. Phenotypically affected males in family 1 had yellowish-brown, poorly mineralized enamel; those in family 2 had thin, smooth, hypoplastic enamel. Heterozygous females in both kindreds had vertical hypoplastic grooves in their enamel. DNA was obtained from family members; exons 1-7 of AMELX were amplified and sequenced. Mutational analysis of family 1 revealed a single-base-pair change of A-->T at nucleotide 256, resulting in a His-->Leu change. Analysis of family 2 revealed deletion of a C-nucleotide in codon 119 causing a frameshift alteration of the next six codons, and a premature stop codon resulting in truncation of the protein 18 amino acids shorter than the wild-type. To date, all mutations that alter the C-terminus of amelogenin after the 157th amino acid have resulted in a hypoplastic phenotype. In contrast, other AMELX mutations appear to cause predominantly mineralization defects (e.g. the mutation seen in family 1). This difference suggests that the C-terminus of the normal amelogenin protein is important for controlling enamel thickness.

Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes.

Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype.