Human cranial vault thickness in a contemporary sample of 1097 autopsy cases: relation to body weight, stature, age, sex and ancestry.

The relation between human cranial vault thickness (CVT) and various elements of the physical anthropological biological profile is subject of ongoing discussion. Some results seem to indicate no correlation between CVT and the biological profile of the individual, whereas other results suggest that CVT measurements might be useful for identification purposes. This study assesses the correlation between CVT and body weight, stature, age, sex, and ancestry by reviewing data of 1097 forensic autopsies performed at the Netherlands Forensic Institute (NFI). In subadults (younger than 19 years of age at the time of death), all frontal, temporal, and occipital CVT measurements correlated moderately to strongly with indicators of growth (body weight, stature, and age). Neither sex nor ancestry correlated significantly with cranial thickness. In adults, body weight correlated with all CVT measurements. No meaningful correlation was found between CVT and stature or age. Females showed to have thicker frontal bones, and the occipital region was thicker in the Negroid subsample. All correlation in the adult group was weak, with the distribution of cranial thickness overlapping for a great deal between the groups. Based on these results, it was concluded that CVT generally cannot be used as an indicator for any part of the biological profile.

Diagnostic dry bone histology in human paleopathology.

Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

Re-examining so-called 'secondary identifiers' in Disaster Victim Identification (DVI): Why and how are they used?

Disaster victim identification (DVI) refers to the identification of multiple deceased persons following an event that has a catastrophic effect on human lives and living conditions. Identification methods in DVI are typically described as either being primary, which include nuclear genetic markers (DNA), dental radiograph comparisons, and fingerprint comparisons, or secondary, which are all other identifiers and are ordinarily considered insufficient as a sole means of identification. The aim of this paper is to review the concept and definition of so-called 'secondary identifiers" and draw on personal experiences to provide practical recommendations for improved consideration and use. Initially, the concept of secondary identifiers is defined and examples of publications where such identifiers have been used in human rights violation cases and humanitarian emergencies are reviewed. While typically not investigated under a strict DVI framework, the review highlights the idea that non-primary identifiers have proven useful on their own for identifying individuals killed as a result of political, religious, and/or ethnic violence. The use of non-primary identifiers in DVI operations in the published literature is then reviewed. Because there is a plethora of different ways in which secondary identifiers are referenced it was not possible to identify useful search terms. Consequently, a broad literature search (rather than a systematic review) was undertaken. The reviews highlight the potential value of so-called secondary identifiers but more importantly show the need to scrutinise the implied inferior value of non-primary methods which is suggested by the terms "primary" and "secondary". The investigative and evaluative phases of the identification process are examined, and the concept of "uniqueness" is critiqued. The authors suggest that non-primary identifiers may play an important role in providing leads to formulating an identification hypothesis and, using the Bayesian approach of evidence interpretation, may assist in establishing the value of the evidence in guiding the identification effort. A summary of contributions non-primary identifiers may make to DVI efforts is provided. In conclusion, the authors argue that all lines of evidence should be considered because the value of an identifier will depend on the context and the victim population. A series of recommendations are provided for consideration for the use of non-primary identifiers in DVI scenarios.

An Investigation of Micro-CT Analysis of Bone as a New Diagnostic Method for Paleopathological Cases of Osteomalacia.

OBJECTIVE: This paper looks to broaden the methodological possibilities for diagnosing osteomalacia in archaeological bone using micro-CT analysis. Increasing the identification of osteomalacia in paleopathology will provide support for important interpretive frameworks. MATERIALS: Nine embedded and two unembedded rib fragments were sourced from St. Martin's Birmingham and Ancaster, UK, and Lisieux Michelet, France. Of the 11 samples, nine were previously confirmed as osteomalacic, and presented with varying levels of diagenesis and two were non-osteomalacic controls, one of which exhibits diagenetic change. METHODS: Micro-CT, backscattered scanning electron microscopy, and light microscopy were employed. Micro-CT images were evaluated for osteomalacic features using corresponding microscopic images. RESULTS: Micro-CT images from osteomalacic samples demonstrated the presence of defective mineralization adjacent to cement lines, areas of incomplete mineralization, and resorptive bays/borders, three key diagnostic features of osteomalacia. Diagenetic change was also detectable in micro-CT images, but did not prevent the diagnosis of osteomalacia. CONCLUSIONS: Micro-CT analysis is a non-destructive method capable of providing microstructural images of osteomalacic features in embedded and unembedded samples. When enough of these features are present, micro-CT images are capable of confirming a diagnosis of osteomalacia. SIGNIFICANCE: Vitamin D deficiency has important health consequences which operate throughout the life course. Increasing the ability to detect cases of vitamin D deficiency provides researchers with a greater understanding of health and disease in past communities. LIMITATIONS: Only adult rib samples were used. SUGGESTIONS FOR FURTHER RESEARCH: Paleopathologists should look to test the utility of micro-CT analysis in diagnosing active rickets in subadult individuals.

Outcome of a rabbit model for late irradiation effects in mandibular oral mucosa and bone: A pilot study.

BACKGROUND/AIM/OBJECTIVE: Late side effects of radiotherapy (RT) in the treatment for head and neck (HN) malignancies involve an inadequate healing response of the distressed tissue due to RT-induced hypovascularity. The aim of this study was to develop a pilot model in which vascular alterations associated with the onset of late irradiation (IR) injury could be measured in rabbit oral mucosa and mandibular bone. MATERIALS AND METHODS: Eight male New Zealand white rabbits were divided over four treatment groups. Group I-III received four fractions of RT (5.6 Gy, 6.5 Gy, and 8 Gy, respectively) and Group IV received 1 fraction of 30 Gy. Oral microcirculatory measurements were performed at baseline (before RT) and once a week during 11 consecutive weeks after RT assessing perfusion parameters, that is, total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI). Post-mortem histopathology specimens were analyzed. RESULTS: Five weeks after RT, TVD, and PVD in all groups showed a decrease of >10% compared to baseline, a significant difference was observed for Groups I, II, and IV (P<0.05). At T11, no lasting effect of decreased vessel density was observed. PPV and MFI remained unaltered at all-time points. Group IV showed a marked difference in scattered telangiectasia such as microangiopathies, histological necrosis, and loss of vasculature. CONCLUSION: No significant lasting effect in mucosal microcirculation density due to IR damage was detected. Observed changes in microcirculation vasculature and histology may align preliminary tissue transition towards clinical pathology in a very early state associated with late IR injury in the oral compartment. RELEVANCE FOR PATIENTS: Enhancing knowledge on the onset of late vascular IR injury in the HN region could help the development, monitoring, and timing of therapies that act on prevention, discontinuation, or repair of radiation pathology.

Dry bone histology of bone tumours.

This article focuses on the application of dry bone histology in the diagnosis of a series of different bone tumours. It provides a short introduction on bone tumour classification and how tumours may affect the skeleton. To illustrate the value of dry bone histology in the diagnostic process we studied the 'fresh' and 'dry' bone histology of a series of well-documented, recent clinical cases of various benign and malignant bone tumours. We show that histology is a valuable instrument to assess bone tissue architecture, which provides information on the biological behaviour of a tumour. Though histology may reveal the specific 'tumorous' bone deposition of high-grade conventional osteosarcomas, all other bone tumours display common, unspecific features. This holds for the following tumours: osteochondroma, hyperostotic meningioma, high-grade angiosarcoma, grade 2 chondrosarcoma, myoepithelial carcinoma, high-grade osteosarcoma and four carcinoma metastases. We conclude that histology is useful in cases where the biological behaviour of a tumour is to be defined, and is particularly an aide in the diagnosis of high-grade conventional osteosarcomas. Nevertheless, the differential diagnosis on the bone tumours in our series should primarily be based on a combination of physical anthropological patient data (age, sex), gross anatomy (e.g. tumour morphology and location), and radiography.

Four possible cases of osteomalacia: The value of a multidisciplinary diagnostic approach.

Rickets and residual rickets are often encountered in Dutch archeological skeletal samples. However, no archeological Dutch paleopathological case of adult osteomalacia has been described in literature to date. This paper describes the first four archeological Dutch paleopathological cases of osteomalacia and assesses the value of the various modalities (macroscopic assessment, radiology and histology) that may be used for diagnosis. The skeletal remains investigated originate from the Meerenberg psychiatric hospital cemetery in Bloemendaal, the Netherlands, and date from 1891 - 1936. The remains of 69 adult individuals were inspected for macroscopic lesions which may be associated with osteomalacia. In cases suspect for osteomalacia, complimentary radiological and histological investigations (BSE-SEM and light microscopy) were performed. Macroscopically, four individuals presented with lesions (highly) suggestive of osteomalacia. Histological examination (both BSE-SEM and light microscopy) provided valuable information to come to an eventual diagnosis of osteomalacia in all four cases. Light microscopy proved to be an feasible alternative for BSE-SEM. The added value of radiological analyses was limited. The individuals identified were most likely patients in the psychiatric hospital, and the reason for their institutionalization and/or the regime in the institution may have played a role in the development of the osteomalacia observed.

Dutch population specific sex estimation formulae using the proximal femur.

Sex estimation techniques are frequently applied in forensic anthropological analyses of unidentified human skeletal remains. While morphological sex estimation methods are able to endure population differences, the classification accuracy of metric sex estimation methods are population-specific. No metric sex estimation method currently exists for the Dutch population. The purpose of this study is to create Dutch population specific sex estimation formulae by means of osteometric analyses of the proximal femur. Since the Netherlands lacks a representative contemporary skeletal reference population, 2D plane reconstructions, derived from clinical computed tomography (CT) data, were used as an alternative source for a representative reference sample. The first part of this study assesses the intra- and inter-observer error, or reliability, of twelve measurements of the proximal femur. The technical error of measurement (TEM) and relative TEM (%TEM) were calculated using 26 dry adult femora. In addition, the agreement, or accuracy, between the dry bone and CT-based measurements was determined by percent agreement. Only reliable and accurate measurements were retained for the logistic regression sex estimation formulae; a training set (n=86) was used to create the models while an independent testing set (n=28) was used to validate the models. Due to high levels of multicollinearity, only single variable models were created. Cross-validated classification accuracies ranged from 86% to 92%. The high cross-validated classification accuracies indicate that the developed formulae can contribute to the biological profile and specifically in sex estimation of unidentified human skeletal remains in the Netherlands. Furthermore, the results indicate that clinical CT data can be a valuable alternative source of data when representative skeletal collections are unavailable.

An accessory skull suture mimicking a skull fracture.

This paper describes an investigation of the sudden and unexpected death of a five-and-a-half-month-old boy. As in every Dutch case of sudden unexpected death in infancy (SUDI), a multidisciplinary diagnostic approach was used. This included post-mortem radiography, showing a linear discontinuity of the parietal bone. Originally this was interpreted as a skull fracture, but autopsy indicated no signs of mechanical trauma. Instead the defect was defined as a unilateral accessory suture of the parietal bone. The initial erroneous diagnosis had severe adverse consequences and thus every health care professional or forensic specialist dealing with paediatric mechanical traumas should be cautious of this rare anomaly.

A lethal case of the dapsone hypersensitivity syndrome involving the myocardium.

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.

Effects of partial ileal bypass on the progression of atherosclerotic lesions in WHHL rabbits.

At age of 40 weeks, 9 WHHL rabbits were necropsied as a baseline control group for evaluating aortic and coronary atherosclerosis. An additional 18 WHHL rabbits of the same age underwent either a partial ileal bypass (PIB) or a sham operation. Serum cholesterol concentrations were significantly lower in PIB rabbits than in sham-operated rabbits, mean postsurgical values being 7.9 +/- 2.3 mmol/l and 13.2 +/- 2.4 mmol/l, respectively. This effect was mainly due to a lower LDL-cholesterol concentration. Serum triglycerides remained unaffected. Thirty weeks after surgery the PIB and sham rabbits were necropsied and atherosclerosis was evaluated. Progression of atherosclerotic plaque size in the sham group was most prominent in the aortic arch. PIB largely prevented this progression. The frequency of plaque complications in the aortic arch also increased in the sham groups. Here, no significant improvement was found in the PIB group. Extensive examination of the heart showed some affected coronary arteries in every 40-week-old WHHL rabbit. Progression of coronary atherosclerosis during the postsurgical period was small in both sham and PIB groups. However, while PIB did not affect the plaque size, it significantly reduced the number of coronary arteries affected.

Does nifedipine suppress atherogenesis in WHHL rabbits?

The effects of the calcium antagonist, nifedipine, on atherogenesis were investigated in WHHL rabbits, a unique animal model for human familial hypercholesterolemia. Nifedipine, in a daily dose of 40 mg, was fed orally to 9 rabbits over a period of 26 weeks, resulting in serum concentrations of between 740 and 1370 ng/ml. Rabbits were killed at an age of 40 weeks and atherosclerotic plaque formation in various aortic segments was quantified. Atherosclerosis was most pronounced in the aortic arch and the thoracic aorta, plaques covering, respectively, 59 +/- 17% and 17 +/- 9% of total vessel area. These results are similar to those observed in a control group, which received the same diet and no nifedipine and displayed lesions on 62 +/- 19% and 21 +/- 13% of total area of aortic arch and thoracic aorta, respectively. Although variations in plaque area between WHHL rabbits are large and thus preclude the observation of small effects, the efficacy of nifedipine as an anti-atherogenic agent in rabbits with hereditary hypercholesterolemia appears questionable.

Partial ileal bypass inhibits atherosclerosis in WHHL rabbits.

The effectiveness of partial ileal bypass (PIB) as a counter-measure against atherosclerosis was evaluated in WHHL rabbits. The effects of PIB and sham operation, each performed in five animals, on serum lipids, lipoproteins and plaque formation were investigated. PIB resulted in an immediate and sustained decrease of 52% (range 29-67%) in serum cholesterol, while sham operation had no effect. The main reduction was in LDL cholesterol; VLDL-cholesterol was lowered to a lesser extent. PIB also appeared to change the electrophoretic behaviour of total serum, very low density and low density lipoproteins. Plaque formation, measured 30 weeks after operation in various aortic segments and arteries, was significantly reduced after PIB. It is concluded that an induced lowering of serum cholesterol can prevent atherosclerosis in WHHL rabbits. Also, these animals must be considered as a model for the receptor-defective cellular phenotype of homozygous familial hypercholesterolemia, not for the receptor-negative type, which is the only truly genetically homozygous form.

Human leukocyte antigen sensitization after cryopreserved human meniscal transplantations.

The presence of antibodies against human leukocyte antigens (HLA) in recipients of cryopreserved, non-tissue-antigen-matched human meniscal allografts was evaluated. Serological HLA typing was performed for both class I and class II antigens. The results showed that 11 of 18 recipients became sensitized.

Autopsy analysis in patients with vascular diseases.

An analysis of autopsy findings in 68 patients who died with vascular surgical disorders was performed. Incorrect diagnoses and therapy were evaluated. It was found that complications of the primary disease or its treatment were frequently missed clinically (41%). Septic complications and severe hemorrhage were common in examinations of morbidity and mortality. In 13% of cases a treatment error with adverse impact on survival was detected. It is concluded that postmortem examination is a valuable tool in the final evaluation of patient care in a vascular surgical unit. A repeated plea for the autopsy is supported by this study.

Hemihepatectomy and transfer of the portal inflow tract of the retained hemiliver in the dog.

The results of resection of cancers arising from the biliary tract or hilar portions of the liver might be improved by concomitant resection of all potentially involved regional lymphatics and vessels in the hepatoduodenal ligament. A method to replace the portal vein before its resection in combination with a hemihepatectomy was developed in 15 dogs. A second hepatic inflow tract for the portal blood was constructed by transposition of the splenic vein to an intrahepatic portal vein branch spared during hemihepatectomy. When this paraportal bypass had been shown to function well, the portal vein could be cut safely. Under the influence of the initially raised portal blood pressure, the bypass expanded in the next several weeks to a vessel almost as wide as the former portal vein, with concomitant normalization of the portal pressure and normal liver regeneration. Replacement of the portal vein as such by an adequate paraportal bypass enhances the resectable area of the liver hilus.

The significance of microcalcifications without palpable mass in the diagnosis of breast cancer.

Microcalcifications constitute an important part of nonpalpable breast lesions and may be the first sign of a breast carcinoma. Between 1975 and 1984, 150 consecutive patients with clusters of at least five microcalcifications without palpable findings as the only indication for biopsy were treated. One hundred seventy-three groups of microcalcifications were excised and 51 malignancies were detected (29.5%). Most of the malignant lesions were noninfiltrating (56%). Axillary or distant metastases occurred in 11% of the fully evaluable cases. This warrants the expectation that these patients have a very favorable prognosis. Breast biopsy for nonpalpable-clustered microcalcifications is a feasible and valuable procedure. Close cooperation is required between the surgeon, radiologist, and pathologist.

Localization and excision of nonpalpable breast lesions. A surgical evaluation of three methods.

Three methods of excising nonpalpable breast lesions have been evaluated: (1) "blind" method, using mammographic coordinates; (2) preoperative localization with the Frank needle; and (3) Frank needle localization aided by a multiperforated compression plate. Successful removal at first attempt occurred in about 80% with any method. The size of the biopsy specimens did not differ significantly among the three groups and is most probably a function of the breast volume. The failure rate was seven (2.1%) of 332 biopsies. Since three of the six repeated biopsies yielded specimens with malignancy, the persistence of a radiographically suspicious lesion on follow-up mammogram of the operated-on breast is an urgent indication for reoperation.

Healing of experimental colonic anastomoses: effect of antineoplastic agents.

The effect of a combination of antineoplastic agents (bleomycin (2 mg/kg/d), 5-fluorouracil (10 mg/kg/d) and cisdiamminedichloroplatinum (0.35 mg/kg/d)), given intravenously, on the healing of colonic anastomoses was investigated in rats. Ninety-six male Wistar rats were divided into four groups. A control group of rats underwent surgery only. The remaining rats were operated either 2 days before, 2 days after or during the 5-day chemotherapy course. In all groups rats were killed after 3, 7 and 21 days. Wound healing of the anastomosis was assessed by measuring the bursting pressures and hydroxyproline contents. Operating in the middle of the 5-day chemotherapy course had the greatest effect on anastomotic healing. This was most apparent on the seventh day postoperatively. When surgery was performed on the second day after the chemotherapy course there was an early delay in wound healing as measured by hydroxyproline content. Seven days postoperatively concentrations were in the same range as those in the control group. Chemotherapy commencing 2 days after surgery did not affect anastomotic healing as compared to the control group. Bursting pressure and hydroxyproline content at the end of the experiment were more or less comparable in all groups.

Diagnosis and treatment of adult intussusception.

Twenty adults were treated for intussusception in two large hospitals from 1969 to 1988. Fourteen intussusceptions originated in the small intestine and 6 in the large intestine. Diagnosis was reached preoperatively in only 10 patients, probably due to the atypical clinical picture. In addition to a high degree of suspicion, careful examination of plain abdominal radiograph and ultrasonography are helpful in diagnosing adult intussusception. In 18 of 20 patients, an organic lesion causing intussusception was found. In six patients the cause was a malignancy. In such cases surgical treatment is necessary. In jejunojejunal and ileoileal intussusceptions, an attempt at primary reduction followed by resection or enterotomy is justified. In most cases of ileocolic, ileocecocolic, and colocolic intussusception, primary resection is the treatment of choice, especially in patients over 60 years old because of the high incidence of malignancy.