Diagnosis of metaphyseal fractures in infants and young children with suspected inflicted injury: a systematic review of cross-sectional imaging techniques.

AIM: To compare the diagnostic accuracy, advantages, and disadvantages of different medical imaging techniques for detecting metaphyseal fractures (also known as classic metaphyseal lesions [CMLs]) in infants and young children with suspected inflicted trauma. MATERIALS AND METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool criteria. Predefined keywords were used to search online databases for English articles published between 1 January 1980 and 31 March 2023. RESULTS: The initial search revealed 83 studies, only five of which met the inclusion criteria. The sensitivity and specificity of positron-emission tomography (PET) were 67% and 99%, respectively. The sensitivity and specificity of ultrasound were 55-61% and 96-97%, respectively. The sensitivity of magnetic resonance imaging (MRI) whole-body screening was 31%. The sensitivity of bone scintigraphy was 17% in one and 35% in a second study. Computed tomography was not used to detect CMLs in any diagnostic accuracy study. CONCLUSION: This systematic review has identified only a small number of relevant studies. In addition to the skeletal survey, PET and ultrasound may be helpful for the diagnosis of CMLs in infants and young children with suspected abuse; however, ultrasound has greater potential than PET due to its higher specificity, lack of radiation exposure, low cost, and wider availability.

The identification of osteopontin as a metastasis-related gene product in a rodent mammary tumour model.

The rat mammary epithelial cell line, Rama 37, yields benign, non-metastasizing adenomatous tumours in syngeneic Furth-Wistar rats. Transfection of this stably diploid cell line with genomic DNA fragments from a human metastasizing breast cancer cell line yields cells which, when injected subcutaneously in syngeneic rats, give rise to secondary tumours in a number of the animals. From one such secondary lung tumour, a cell line was established designated Ca2-5-LT1. This cell line, when introduced into the syngeneic rat host, also showed the ability to metastasise. To determine key changes in gene expression that occur during the progression from Rama 37, the benign tumour-inducing cell line, to the metastatic derivative Ca2-5-LT1, a general method of subtractive hybridization has been employed. This procedure in conjunction with Northern blotting and nucleic acid sequencing has been used to identify mRNAs expressed differentially between the metastatic and nonmetastatic cell lines described above. So far, of the subtracted cDNAs that have been identified which represent differentially expressed mRNAs, a large proportion of these cDNAs corresponded to the mRNA for rat osteopontin (OPN). The mRNA for OPN was expressed at a ninefold higher level in the metastatic Ca2-5-LT1 cell line when compared to the nonmetastatic parental Rama 37 cell line. Rama 37 cells transfected with DNA from a human benign cell line failed to show elevated levels of OPN mRNA. Following transfection of Rama 37 cells with an expression-construct producing elevated levels of OPN, the newly-transfected cells, when introduced into the rat host, developed metastases in 55% of the animals that produced primary tumours. These experiments show that increasing the expression of OPN in a previously benign cell tine is sufficient to produce a metastatic phenotype in this particular rat mammary model.

Isolation of and effector for metastasis-inducing DNAs from a human metastatic carcinoma cell line.

Benign rat mammary epithelial cells transfected with restriction enzyme-fragmented DNA from a human malignant metastatic cell line (Ca2-83) produces transfectants that yield metastatic tumours in syngeneic rats. The six metastasis-inducing DNAs (Met-DNAs) that have been isolated from such transfectants are subgene in size and do not code for any expressed mRNAs, but correspond to potential regulatory regions of human DNA from malignant, metastatic cells. In pilot studies the one Met-DNA tested is detectable in some human breast tumours but not in normal tissue. Transfection of all six Met-DNAs singly into the benign mammary epithelial cells causes enhanced expression of osteopontin, whilst transfection of cDNA for osteopontin also induces the metastatic state. These results show that short regulatory DNAs exist in human cancer cells that can induce metastatic spread via a common effector gene, osteopontin, in model rat mammary cell lines.

Patient decision-making in relation to extensive restorative dental treatment. Part II: Evaluation of a patient decision-making model.

A theoretical model was proposed and tested to evaluate some of the factors involved in patients' decisions to undergo extensive restorative dental treatment. This model incorporates aspects of the environment within which the decision occurred (the patient/provider relationship, social influence and the role of cues in initiating treatment) and internal values held by the individual (perceptions of value of and barriers to treatment). Value of treatment was measured using aesthetics, function, health motivation and self-esteem. Barriers to treatment included fears and anxieties about treatment, the costs of treatment, the time involved in obtaining treatment and access to care. Data were collected by mailed questionnaire from 188 patients at a North American state university dental school who had received over $1,500 of restorative dental treatment during 1990/91. Data were analysed using path analysis multiple regression. The most important determinant in the decision to undergo treatment was patient/provider relationship. As expected, barriers exerted an inverse effect upon the outcome and had twice the influence compared with the patients' perceived value of treatment. Cues and social influence were not shown to play a significant role in initiating restorative dental treatment.

Patient decision-making in relation to extensive restorative dental treatment. Part I: Characteristics of patients.

This paper presents descriptive and demographic data gathered in response to a mailed questionnaire of 188 patients at the University of Michigan School of Dentistry who had incurred costs of at least $1500 on restorative dental treatment between January 1990 and december 1991. The development and testing of the behavioural model used is described in part II. Descriptive information included primary reason for treatment, cues to treatment, previous attendance, aspects of the patient/practitioner relationship, treatment costs, satisfaction with appearance and insurance coverage.

The role of osteopontin in tumorigenesis and metastasis.

Osteopontin (OPN) is a calcium-binding phosphoprotein which is believed to play a role in several different and apparently distinct cellular processes. Recently, expression of OPN has been linked to tumorigenesis and metastasis in several experimental animal models and human patient studies. Precisely what role OPN plays in these processes is far from clear. OPN is known to importantly contribute to cell adhesion interactions, possibly mediated by the highly conserved GRGDS amino acid sequence, a motif found on a number of proteins which play a role in cell adhesion. In addition, OPN has binding affinity for several different cellular receptors, potentially allowing it to stimulate various signaling pathways and influence distinct cellular events which may ultimately favor tumorigenesis or metastasis.

The isolation of CpG islands from human chromosomal regions 11q13 and Xp22 by segregation of partlymelted molecules.

We isolated fragments containing parts of CpG islands from human chromosomal regions chosen for expected differences in gene density by segregation of partly melted molecules. Restriction fragments of P1 bacteriophage clones covering a region of 11q13 and those of cosmid clones derived from Xp22 were recovered from bands in denaturing gradient gels that were retained following prolonged exposure to electric field. Forty-five independent fragments derived from 11q13 and five from Xp22 were isolated. Nucleotide sequence analysis revealed that 11 of the 45 fragments from 11q13 contained CpG islands including four derived from known genes in 11q13. None of the five fragments derived from Xp22 resembled CpG islands. The number of CpG island fragments obtained was consistent with the expectation based on the number of Not I restriction endonuclease sites present at these regions. Adjustment of parameters in our quasi-theoretical approach to the rate of fragment dissociation improves the discrimination between retention and non-retention. The results support probable identification of CpG island fragments by their reduced rate of strand dissociation when retarded in a denaturing gradient gel.

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R), a putative breast tumor suppressor gene.

Loss of heterozygosity (LOH) at the mannose 6-phosphate/insulin-like growth factor 2 receptor gene locus (M6P/IGF2R) on 6q26-27 has recently been demonstrated in approximately 30% of both invasive and in situ breast cancers. LOH was coupled with somatic point mutations in the remaining allele in several instances, leading to the proposition that M6P/IGF2R is a tumor suppressor gene. Somatic mutations in M6P/IGF2R have also been described in hepatoma and gastrointestinal cancers with the replication error positive (RER+) phenotype. These data indicate that M6P/IGF2R loss of function mutations may be involved in the pathogenesis of a wide spectrum of malignancies. Extensive data on the normal function of the M6P/IGF2R suggest that loss of M6P/IGF2R activity may contribute to multiple aspects of tumor pathophysiology, including deregulated growth, apoptosis, angiogenesis and invasion.