A study of osseointegrated dental implants following cremation.

BACKGROUND: The comparison of dental morphology and restorative work for human identification has been well documented. This case study involved documentation of osseointegrated and clinically restored dental implants following cremation. METHODS: The mandible and the maxilla were excised from a head containing implants and cremated. The remains were retrieved, digital and radiographic images were taken and elemental analysis undertaken. The brand of implants was identified utilizing web based search engines. A prosthodontist, known to commonly use this implant system, was approached to ascertain possibilities that matched the data given. RESULTS: Following cremation the implants were identified and a prosthodontist was able to identify the deceased. Two implants in the maxilla had dehiscences on their buccal surfaces, which could not be detected by periapical radiographs. CONCLUSIONS: Dental implants osseointegrated and restored with a prosthetic superstructure were recognizable following severe incineration. It was possible to trace back the identity of the unknown victim to a prosthodontist. Bone dehiscences discovered in this study highlighted how two-dimensional radiographs may not reveal lack of bone support.

Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study.

BACKGROUND: Case control studies suggest that genetic thrombophilias increase the risk of placenta-mediated pregnancy complications (pregnancy loss, small for gestational age (SGA), preeclampsia and/or placental abruption). Cohort studies have not supported this association but were underpowered to detect small effects. OBJECTIVE: To determine if factor V Leiden (FVL) or the prothrombin gene mutation (PGM) were associated with placenta-mediated pregnancy complications. PATIENTS/METHODS: A prospective cohort of unselected, consenting pregnant women at three Canadian tertiary care hospitals had blood drawn in the early second trimester and were genotyped for FVL and PGM after delivery. The main outcome measure was a composite of pregnancy loss, SGA < 10th percentile, preeclampsia or placental abruption. RESULTS: Complete primary outcome and genetic data were available for 7343 women. Most were Caucasian (77.7%, n = 5707), mean age was 30.4 (± 5.1) years, and half were nulliparous. There were 507 (6.9%) women with FVL and/or PGM; 11.64% had a placenta-mediated pregnancy complication. Of the remaining 6836 women, 11.23% experienced a complication. FVL and/or PGM was associated with a relative risk of 1.04 (95% CI, 0.81-1.33) for the composite outcome, with similar results after adjustment for important covariates. CONCLUSIONS: Carriers of FVL or PGM are not at significantly increased risk of these pregnancy complications.

The significance of bruising in infants--a forensic postmortem study.

OBJECTIVE: To determine the significance of bruises in cases of infant death to ascertain if their presence was associated with other injuries or homicide. DESIGN: Retrospective cohort study. SETTING: Forensic Science South Australia, Adelaide, South Australia, Australia. PATIENTS: 135 infants aged between 7 and 364 days autopsied over a 9-year period from June 1999 to May 2008. OUTCOME MEASURES: Coronial forensic autopsy reports. METHODS: Examination of autopsy reports to determine how many infants had bruising and whether bruising was associated with other injuries or lesions of concern. Cause and manner of death were also recorded. RESULTS: There were 83 boys and 52 girls. Twenty-one infants (15.6%) had one or more bruises, and 114 had no bruises. In the group of 21 infants with bruises, 17/21 had other injuries/lesions (81%), with 5/21 homicides (24%). Of the 114 non-bruised infants, only 9 (8%) had other injuries/lesions with only 4 homicides (3.5%). The incidence of other injuries/lesions was significantly higher in bruised infants compared with the non-bruised group (p<0.001), as was the occurrence of homicide (p=0.003). Bruises were found in 15.6% of infants presenting to coronial autopsy, with a sensitivity of 65% and a specificity of 96% as markers for other injuries (positive predictive value 0.81; negative predictive value 0.92). At <6 months of age, this increased to a sensitivity of 71%, with a similar specificity of 95%. CONCLUSIONS: Bruising is a significant marker for other injuries in infants presenting to coronial autopsy. Homicide occurs more commonly in this group.

A regression model to predict warfarin dose from clinical variables and polymorphisms in CYP2C9, CYP4F2, and VKORC1: Derivation in a sample with predominantly a history of venous thromboembolism.

BACKGROUND: Pharmacogenomic warfarin dosing has been suggested to produce more accurate dosing and an improved patient safety profile; however, very few models have been derived in patients with venous thromboembolism. We sought to develop a new algorithm to predict maintenance dose in a cohort of patients, using clinical variables and genetic polymorphism in CYP2C9, VKORC1, and CYP4F2. METHODS: Patients on a stable maintenance dose of warfarin, with observed dose ranging from 0.6 to 12mg were recruited from a specialized anticoagulation clinic (Ottawa Hospital Thrombosis Clinic) with genotyping and standardized patient interviews being conducted to collect clinical and genomic variables known to impact warfarin dose. Multivariate linear regression was used to develop the model using a stepwise backwards elimination approach. RESULTS: From 249 enrolled patients with a mean clinical maintenance dose of 5.58mg/day, a model with an R(2) of 58% was developed as: Dose=1.85-0.048(Age)+0.041(BMI)+0.05(Height in cm) - 0.73(Less Exercise) - 1.13(2C9*2 Hetero) - 2.09(2C9*2 Homo) - 1.51(2C9*3 Hetero) -1.43(VKORC1 GA) - 2.86(VKORC1 AA) - 1.33(4F2 CC) -1.24(4F2 CT) - 1.46(Angiotensin II Receptor Antagonist) - 0.84(beta-Blockers). Analysis of residual plots revealed that prediction errors were a function of observed maintenance dose with the model tending to predict higher doses than observed in those with low dose requirements and lower doses than observed in those with higher dose requirement. CONCLUSION: Our study confirms the importance of the CYP4F2 polymorphism. Our model may prove useful in clinical practice but further validation studies are required before implementation into clinical practice.

Cognitive and behavioural effects of genetic testing for thrombophilia.

Very few studies have examined the impact of genetic testing for thrombophilia on health behaviours, perceptions of control over risk factors for venous thromboembolism, or health services utilization. Through a postal questionnaire we compared first degree relatives with thrombophilia (carriers) most of whom had received counseling, to those without (non-carriers) with respect to: (a) perceived causes of venous thromboembolism; (b) perceived control; (c) health behaviour changes; and (d) use of health care services. 44/51 for carriers and 26/47 for non-carriers completed questionnaires. Carriers were more likely to believe their risk of venous thromboembolism 'is a little higher' or 'much higher' than average (p < 0.001) but some continued to believe their risk 'is the same as' or 'lower than' average. 16%-32% of carriers did not recognize major risk factors. Stress, worry, or depression, negative attitude, and over-exertion were over-interpreted as risks. 37.2% did not appreciate that thrombophilia increases risk. Behaviour changes were uncommon. There is a need for research on education and strategies to improve knowledge in thrombophilia carriers.

The science behind the quest to determine the age of bruises-a review of the English language literature.

Bruises are common injuries that can have medicolegal significance. There are those that maintain it is not possible to estimate the age of bruises. However, appreciation of the biological processes related to the resolution of a bruise suggests that these may provide information regarding the age of a bruise. Potential methods for determining the age of bruises-visual observation, colorimetry, spectrophotometry and histology-are reviewed. The observation of yellow (not orange or brown) indicates a bruise is not recent, but the abilities of visual observation are limited by the physiology of the human eye. Analysis of spectrophotometric data may provide more useful and objective information. Histological examination may be appropriate only in the postmortem situation. The lack of published information limits this as a tool for estimating the age of bruises. It is not known how the wide range of factors that can influence bruise formation and resolution could affect estimation of bruise age.

Firearm fatalities in Western Sydney 1994-2003.

This study reviews firearm-related deaths (homicidal, suicidal and accidental) from 1994 to 2003 in the Western Sidney area, Australia, serviced by the Westmead Department of Forensic Medicine, in order to document the features of the cases and to assess the effect of the introduction of the NSW Firearms Act in 1996. There were 211 fatalities involving firearms (1.8% of all of the Coroner's cases for the period); firearm deaths were classified as homicide (75), suicide (134) or accidental (2). There was a clear peak of homicide deaths by firearm in the 20-29 age group, whereas the suicide peak was broad, spanning the ages 20-69 years. More suicides occurred at home than homicides and a higher proportion of suicides were by rifle than homicides, which favoured hand guns. Entry wounds in suicides mostly involved the head, with the chest being the commonest entry site in homicides. The only statistically significant trend was for an increase in the number of firearm-related suicides in males, comparing the number of deaths pre- and post-firearm law introduction. The study includes reports of two suicides by unusual weapons: a home-made pipe gun and a spear gun.

Alternative light source (polilight) illumination with digital image analysis does not assist in determining the age of bruises.

The age of a bruise may be of interest to forensic investigators. Previous research has demonstrated that an alternative light source may assist in the visualisation of faint or non-visible bruises. This project aimed to determine if an alternative light source could be utilised to assist investigators estimate the age of a bruise. Forty braises, sustained from blunt force trauma, were examined from 30 healthy subjects. The age of the bruises ranged from 2 to 231 h (mean = 74.6, median = 69.0). Alternative light source (polilight) illumination at 415 and 450 nm was used. The black and white photographs obtained were assessed using densitometry. A statistical analysis indicated that there was no correlation between time and the mean densitometry values. The alternative light source used in this study was unable to assist in determining the age of a bruise.

The perception of yellow in bruises.

For forensic purposes, the presence of the colour yellow in a bruise may be regarded as indicating it is not recent. However, a previous study has shown that observers may disagree in their description of the colours in a bruise. This study was designed to determine how consistent observers are in perceiving the presence of yellow. Subjects were shown a series of photographs of a bruise that had been digitally modified (Adobe Photoshop) to contain amounts of yellow that increased from 2% to 20%. The point at which subjects first perceived the colour yellow was recorded. The perception threshold for yellow ranged from 4% to 16% (mean=8.7%, median=8%) in the 50 subjects that had normal colour vision. Statistical analysis indicated that an individual's yellow perception threshold increased by 0.07% each year, but gender had no effect. The results reveal that there is variability in the perception threshold for yellow in the general population and that a subject's ability to perceive yellow in a bruise declines with age.

The practical application of reflectance spectrophotometry for the demonstration of haemoglobin and its degradation in bruises.

AIMS: To develop a non-invasive method to demonstrate the presence of haemoglobin and its degradation products in bruises in live human subjects for the purposes of objectively assisting in the determination of the age of a bruise. METHODS: The cuvette holder unit of a Cary 100 Bio UV-Visible Spectrophotometer was replaced with the manufacture's fibre optic cable and optical reflectance probe. The probe was placed on the skin surface. The absorption spectrum from 780 to 380 nm was collected and transformed into the first derivative. Calculation of the first derivative permits absorption attributed to haemoglobin degradation (primarily to bilirubin, but also haemosiderin) to be separated from absorption by haemoglobin. First derivative and colorimetry values, expressed as CIEL*a*b data, were derived from scans of 50 bruises. RESULTS: The fibre optic cable and probe allowed the spectrophotometer to collect reproducible absorption spectra of bruises in the skin of living subjects. A bruise at three days has greater negative first derivative values at 480 and 490 nm than does a fresh bruise, indicating the local degradation of haemoglobin. Correlation between the first derivative and the CIEL*a*b "b" values in a series of bruises indicates that the yellow colour in a bruise is proportional to the amount of local haemoglobin breakdown. CONCLUSION: The ability to demonstrate the presence of haemoglobin and measure its degradation in bruises in living human subjects by a non-invasive method has not been described previously, and may be of use in the objective ageing of bruises for forensic purposes.

Synthesis and cytotoxicity on sensitive and doxorubicin-resistant cell lines of new pyrrolo[2,1-c][1,4]benzodiazepines related to anthramycin.

A new 7,8-methylenedioxy analogue (4) of (+)-porothramycin B (2) and its water-soluble sodium bisulfite derivative (15) have been synthesized in high yields and have been shown to exhibit high cytotoxic activities against several tumor cell lines. The new pyrrolo[2,1-c][1,4]benzodiazepine 4 was as effective against the resistant cell lines as against the doxorubicin-sensitive cell lines tested.

Apoptosis and prognosis in cancer: rationale and relevance.

Apoptosis is the biological process by which cells in tissues undergo programmed death. This process is morphologically identifiable and characterised by light and electron microscopy. However, the biological mechanisms underlying this process, as yet, are poorly understood and in need of elucidation. As apoptotic tumour cells can be identified and counted by light microscopy, there has been interest in the application of the enumeration of apoptosis in malignant growths as a putative prognostic marker. This review outlines the rationale for and discusses the relevance of using such an approach in clinical practice.

Evidence for Fas counter attack in vivo from a study of colorectal cancer.

Peritumoural cytotoxic lymphocytic infiltrates in colorectal carcinoma may attack tumour cells by expressing Fas ligand and inducing tumour cell apoptosis. However, tumours may mount a by down regulating their Fas pathway and expressing Fas ligand themselves to induce apoptosis of lymphocytes. This study used immunohistochemistry to demonstrate the presence of CD8+ lymphocytes and Fas ligand. The score of CD8+ peritumoural lymphocytes was negatively correlated with the Fas ligand score of the tumour. The results provide evidence for the Fas theory, but further work would be required to determine if this is a significant factor in the tumour-host interaction.

Regulation of bovine satellite cell proliferation and differentiation by insulin and triiodothyronine.

Satellite cells activity contributes to postnatal muscle growth. Herein, we have studied the respective influence of insulin and triiodothyronine (T3) on the proliferation and differentiation of primary bovine satellite cells isolated from Semitendinosus muscle of Montbéliard steers. Under basal conditions, satellite cells proliferated until the fifth day of culture, began to fuse into myotubes and expressed differentiation markers such as connectin, myogenin, and myosin heavy chain (MHC) isoforms. Insulin behaved as an effective mitogen. Moreover, it promoted extensive myotube formation and enhanced differentiation as shown by an increase in the accumulation of differentiation markers. Maximal differentiation occurred with insulin physiological range concentrations. A delay in the stimulation of differentiation was registered with a high dose that promoted maximal proliferation. Conversely, T3 decreased cell proliferation in a dose-dependent manner. In addition, fusion and biochemical differentiation (accumulation of connectin, MyoD1, myogenin, and myosin heavy chain isoforms) were also enhanced. Bovine satellite cells seemed to respond differentially to insulin and T3 for proliferation. Interestingly, both hormones displayed a myogenic influence. Our observations suggest that both hormones could influence bovine satellite cells in vivo and contribute to the regulation of postnatal muscle growth.

NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer.

NM23 gene product is a putative metastases suppressor gene which has structural homology to a nucleoside diphosphate kinase. Previous studies examining the relationship between NM23 gene product expression and survival in patients with colorectal cancer have revealed conflicting results. However, no study has focused on young patients with colorectal cancer. This study was carried out to determine if expression of the NM23 gene product was correlated with metastatic potential and survival in young patients (45 years and under) with colorectal cancer. Eighty- one patients with colorectal cancer were studied and the presence of the NM23 gene product (H1) was detected using standard immunohistochemical techniques. NM23 gene product expression did not correlate with tumour stage, lymph node involvement by tumour, presence of distant metastases, extramural vascular invasion or degree of tumour differentiation. Independent risk factors for overall survival were: Dukes' stage (p=0.00001) and extramural vascular invasion (p=0.003). NM23 expression was not an independent prognostic indicator (p=0.55). Therefore, NM23 expression does not correlate with existing indicators of tumour aggressiveness and behaviour nor is it an independent predictor of survival in young patients with colorectal cancer.

Application of the principle of marginal analysis to sampling practice using prostatic chippings as a model.

AIMS: To demonstrate an application of health economic principles in histopathology by using the sampling of transurethral resections of prostate specimens. By demonstrating how marginal costs are calculated the aim is to illustrate that the potential opportunity cost of sampling entire specimens is much greater than would be anticipated by taking average cost, or the cost of producing a histological section alone. METHOD: A mathematical model is used with data obtained from the Aberdeen pathology department files and published estimates of the likely percentage of cancerous chippings in each specimen. RESULTS: The average cost of each cancer detected remains low, between 47 Pounds and 151 Pounds, in all the scenarios examined. However, the marginal costs can become high, exceeding 10,000 Pounds in larger specimens, if all the chippings are processed. CONCLUSIONS: This study demonstrates that there are potential opportunity cost penalties to histopathological services associated with sampling strategies. Although the results are derived from a hypothetical mathematical model using local data that applies only to histopathology, the method could be widely applied. The principles of marginal analysis should be performed by multidisciplinary teams and include outcomes as well as a broader range of costs, including those that arise subsequent to diagnosis.

Angiosarcoma of the penis.

Sarcoma of the penis is rare. We report an angiosarcoma that was essentially an incidental finding, despite the presence of metastatic lesions, in a 46-year-old man who presented with hematemesis and melena. The diagnosis of the primary lesion was confirmed by histology, and the presence of secondary lesions by fine needle aspiration cytology. The patient was given one dose of chemotherapy, but died of a myocardial infarction before being able to receive further treatment. The literature pertaining to this very unusual lesion is discussed.