Porotic hyperostosis: new evidence to support the anemia theory

The etiology of skull lesions known as porotic hyperostosis has long been a matter for speculation. The most widely accepted theory at present suggests that an anemia, either acquired or genetic, is responsible for lesion development. However, acceptance of this theory is not universal and the nature of the relationship between orbital and vault lesions remains a controversial issue. This paper provides a much broader field of supportive evidence on which to base the anemia theory. This involves a synthesis of information from the clinical and anthropological literature as well as new data from two skeletal collections: Poundbury Camp, a Romano-British series, and the Hodgson collection, a 19th century East Asian series. A comparison is made between clinical and anthropological data at the macroscopic, microscopic, radiographic, and demographic levels of analysis. This approach reveals the similarities in expression between clinically diagnosed anemias and porotic hyperostosis.     

The causes of porotic hyperostosis and cribra orbitalia: A reappraisal of the iron‐deficiency‐anemia hypothesis

Porosities in the outer table of the cranial vault (porotic hyperostosis) and orbital roof (cribra orbitalia) are among the most frequent pathological lesions seen in ancient human skeletal collections. Since the 1950s, chronic iron‐deficiency anemia has been widely accepted as the probable cause of both conditions. Based on this proposed etiology, bioarchaeologists use the prevalence of these conditions to infer living conditions conducive to dietary iron deficiency, iron malabsorption, and iron loss from both diarrheal disease and intestinal parasites in earlier human populations. This iron‐deficiency‐anemia hypothesis is inconsistent with recent hematological research that shows iron deficiency per se cannot sustain the massive red blood cell production that causes the marrow expansion responsible for these lesions. Several lines of evidence suggest that the accelerated loss and compensatory over‐production of red blood cells seen in hemolytic and megaloblastic anemias is the most likely proximate cause of porotic hyperostosis. Although cranial vault and orbital roof porosities are sometimes conflated under the term porotic hyperostosis, paleopathological and clinical evidence suggests they often have different etiologies. Reconsidering the etiology of these skeletal conditions has important implications for current interpretations of malnutrition and infectious disease in earlier human populations. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

Evidence of pathological conditions in the Florisbad cranium

Palaeopathological studies of the middle Pleistocene cranium from Florisbad (Free State, South Africa) document the presence of extensive cortical lesions and areas of thinning, a widened medullary cavity with destruction of the diploë, orbital roof lesions, a benign ectocranial neoplasm, and evidence for alveolar destruction, resorption, and antemortem tooth loss. Differential diagnosis suggests one or more possible aetiologies, including a haematological disorder, metabolic condition(s), Paget’s disease of bone, or non-specific infection perhaps following trauma. Moreover, if not directly associated with those on the external vault, orbital lesions alone could have been caused by infection or an indeterminable factor such as pressure from an enlarged organ. Multiple parasagittal lesions on the internal vault cortex probably represent expansile lesions left by enlarged arachnoid granulations. A multifactorial model of pathogenesis may be most appropriate to account for dentoalveolar lesions and antemortem tooth loss. Additionally, there are clear indications of diagenetic alteration deep within the vault, as well as multiple signs of degeneration on the cranium. These complicate the assessment of pathological alterations and identification of their possible aetiology. The Florisbad cranium is the latest specimen to join the growing sample of Pleistocene hominin remains with non-fatal and non-trivial pathological disorders adding to understanding of early human ecology and lifestyle.     

Intentional cranial vault deformation and induced changes of the cranial base and face

Three morphologically distinct populations of Peruvian crania (n = 130) were metrically analysed to quantify changes resulting from intentional artificial vault deformation. Two of these samples are artificially deformed (anteroposterior [AP] and circumferential [C] types). Measurements taken from lateral radiographs demonstrated that alternative forms of the cranial base angle (N-S-Ba, planum angle, planum sphenoidale to plane of the clivus and PANG angle, planum sphenoidale to basion-sella plane) and the orbital and OANG angles (orbital roof to plane of the clivus and basion-sella plane, respectively) of both deformed groups increased while the angle S-Ba-O decreased significantly with respect to the undeformed (N) sample. Changes in the AP group are largely due to anteroinferior displacement of the basion-sella plane. Similar changes in group C are amplified by this group's posterosuperior frontal migration. This migration results in a relatively shallow orbit at the orbital plate/frontal squama interface. Unlike the deformation experienced by the external vault plates, the basion-sella plane orientation remains stable with respect to the Frankfort Horizontal. Additionally, nasal region measurements such as maximum nasal aperture breadth and nasal height were largely stable between each deformed group and the undeformed group. However, facial (bimaxillary and bizygomatic), basicranial, cranial, and frontal breadths decreased significantly from group AP to group N to group C. Thus, gross morphological facial changes between each undeformed group and the control group are largely accounted for by dimensional changes in peripheral structures. These results stress the importance of the dynamic interrelationship between the cranial vault and base in the development of the craniofacial complex.     

Biomechanical models of the human skull: stability of various segments in three simulations

Three simulations by a computer model of human skull, implemented on finite elements and virtual works principles, were performed by a 15 Kg loading of the structure according rules of mechanical stresses of chewing. First model had all elements in place, second was without vault and third was without orbital walls. Stability of the structure was evaluated in terms of "instability coefficient" as an index of sum of moduli and number of considered nodes such moduli give spatial displacement of nodes after loading and deformation of shell elements. All parts of the structure are involved in ensuring stability so that it decreases as different segments or elements are not considered during simulation. The vault plays a great role in total stability of the model while orbital walls appear as a mechanical link between anterior (frontal) and posterior (occipital) parts of the model.     

Effects of fronto-occipital artificial cranial vault modification on the cranial base and face.

Artificial reshaping of the cranial vault has been practiced by many human groups and provides a natural experiment in which the relationships of neurocranial, cranial base, and facial growth can be investigated. We test the hypothesis that fronto-occipital artificial reshaping of the neurocranial vault results in specific changes in the cranial base and face. Fronto-occipital reshaping results from the application of pads or a cradle board which constrains cranial vault growth, limiting growth between the frontal and occipital and allowing compensatory growth of the parietals in a mediolateral direction. Two skeletal series including both normal and artificially modified crania are analyzed, a prehistoric Peruvian Ancon sample (47 normal, 64 modified crania) and a Songish Indian sample from British Columbia (6 normal, 4 modified). Three-dimensional coordinates of 53 landmarks were measured with a diagraph and used to form 9 finite elements as a prelude to finite element scaling analysis. Finite element scaling was used to compare average normal and modified crania and the results were evaluated for statistical significance using a bootstrap test. Fronto-occipitally reshaped Ancon crania are significantly different from normal in the vault, cranial base, and face. The vault is compressed along an anterior-superior to posterior-inferior axis and expanded along a mediolateral axis in modified individuals. The cranial base is wider and shallower in the modified crania and the face is foreshortened and wider with the anterior orbital rim moving inferior and posterior towards the cranial base. The Songish crania display a different modification of the vault and face, indicating that important differences may exist in the morphological effects of fronto-occipital reshaping from one group to another.     

Elaeophorosis in Barbary sheep and mule deer from the Texas Panhandle

Adult Elaeophora schneideri were recovered from the common carotid artery and its branches in 14 of 14 mule deer, Odocoileus hemionus, and 3 of 9 Barbary sheep or aoudads, Ammotragus lervia, from Palo Duro Canyon in the Texas Panhandle. Gross cutaneous lesions attributable to elaeophorosis in the Barbary sheep varied from small circumscribed scars up to 10 cm in diameter usually on the poll or orbital region to extensive proliferative irregular encrustations on the frontal, temporal and orbital regions, sometimes extending to the ears and muzzle. Individual lesions varied from slate-gray scarred areas to brown proliferative edematous and hyperemic encrustations, sometimes with depigmented pustules a few millimeters in diameter. Microscopic lesions ranged from granulation tissue to severe pyogranulomatous reactions with neutrophils, eosinophils, lymphocytes and plasma cells as the primary infiltration. Foreign body giant cells and/or microfilariae were not observed. Microscopic changes in the carotid arteries and their branches were limited to small villous projections on the intimal surface apparently resulting from medial hyperplasia. Cutaneous lesions attributable to elaeophorosis were not observed in mule deer. Histopathologic lesions in the carotid arteries of mule deer were similar to those observed in Barbary sheep. The comparative pathology of elaeophorosis in various hosts is reviewed and discussed in terms of its pathology in Barbary sheep. The potential ramifications of this infection on the expanding aoudad population in the southwestern United States require that elaeophorosis be considered in the management of this species, particularly in areas with sympatric mule deer populations.     

Cranial capacity/cranial base relationships and prediction of vault form: A canonical correlation analysis

Canonical correlation analysis was used to test an hypothesized morphological relationship between vault form and cranial capacity relative to length of the chondrocranium. Ninety-five adult male Czech skulls were measured for vault form expressed as length, width and height of the brain case; the chondrocranium was represented by nasion-basion and basion-opisthion lengths. In terms of explained variation, the first and most important dimension of covariation between vault and chondrocranial variables was size. The second most significant dimension of covariation expressed the hypothesized shape relationships—i.e., overall size being equal, the shorter the chondrocranial base relative to cranial capacity, the shorter and wider the vault. Furthermore, the competing hypothesis that vault form is determined by facial length proved untenable since facial length was predictive of vault shape only when measured as prosthion-basion, a measure that incorporates basal length. When corrected for basal length, facial length is unrelated to vault form. The results are consistent with the assumption that phylogenetic and microevolutionary trends toward brachycephaly in man stem from changes in the relationship between two components of skull growth, the chondrocranial base and the brain.     

Clearing tau pathology with Abeta immunotherapy--reversible and irreversible stages revealed

The report by Oddo and colleagues in this issue of Neuron demonstrates for the first time that clearance of amyloid also results in the removal of early-stage tau pathology in mice that develop both amyloid plaques and neurofibrillary tangles (NFT), the two hallmark lesions of Alzheimer's disease (AD). This result supports a primary role for Abeta in AD etiology.     

The influence of artificial cranial vault deformation on the expression of cranial nonmetric traits: its importance in the study of evolutionary relationships

Nonmetric cranial traits have been commonly used in evolutionary relationship studies. They develop during the growth and development of an individual, and for this reason its expression presents different sources of genetic and nongenetic variation. However, the use of these features in evolutionary relationship studies carries the implicit assumption that much of the nonmetric trait variation is essentially genetic. Among the nonheritable factors, cranial vault deformation has been the most studied in human populations. Because of the widespread distribution and elevated rate of artificial cranial vault deformation found in America, and the importance of nonmetric traits in evolutionary relationship studies in this area, the objectives of this paper are as follows: (a) to study the influence of artificial cranial vault deformation on the presence of nonmetric traits within samples of human craniofacial remains; and (b) to establish artificial cranial vault deformation influence on evolutionary relationships between local populations on a regional scale. Our results indicate that artificial cranial vault deformations alter the variation and covariation of metric and nonmetric traits in some samples. Wormian bones, placed in cranial vault sutures, are the most influenced by this factor. However, our results suggest that when all nonmetric traits were used the artificial cranial vault deformation did not influence the basic pattern of variation among samples. The exclusion or inclusion of wormians bones in evolutionary relationships analysis did not modify the results, but using only wormians bones lead to inconsistent results indicating that these traits have little value on these kind of studies.     

华北人欧洲人和澳洲土著人的头骨厚度

The thickness of the cranial vault at the midline on the mid-frontal squama, pre-bregmatic einence, frontal at bregma, parietal at vertex, occipital at lambda and the external occipita1 protuberance was recorded in 40 male and 7 female Northern Chinese crania, 47 male and 52 female Australian Aboriginal crania and 13 male European crania using specially nodified vernier calipers. Comparison of vault thickness data obtained through direct measurement with those obtained fron lateral radiographs indicated that direct measurenent provided consistently more accurate results.
Male and fermale samples were processed separately so that the extent of sexbased variation could be examined.Student's t test was used to compare the sample means and the percentage of sexual dimorphism for each dimension was calculated according to Garn et al, (1964).The possibility of an allometric association between the thickness of the bones within the cranial vault, size of the cranial vault and stature was examined using Spearman's rank correlation coefficient and the Australian Aboriginal sample.
All but one of the mean thickness dimensions in the Australian Aboriginal male sample is significantly greater than the Northern Chinese and European means. The female results support those obtained with the males.In both males and females thickness at the external occipital protuberance, in all of the populations examined,did not correlate highly with that obtained from other parts of the cranial vault.This reflects the high degree of morphological variation in the position of the internal occipital protuberance and its influence on cranial vault thickness dimensions recorded at the external occipital protuberance.The European and Northern Chinese samples have similar cranial vault thickness dimensions. The Spearman's rank correlation coefficient matrix scores provide sone support for a biological association between vault thickness and overall cranial size. However, there appears to be little support for an association between stature and cranial vault thickness. The difference between the male and female mean vault thickness dimensions were significant at bregma, vertex and the external occipital protuberance in Australian Aboriginals and lambda and the external occipital protuberance in Northern Chinese. Some caution is needed in the interpretation of the Northern Chinese female data as the sample is extremely small.
Evidence of trauma, supressed fractures, is extremely common on the vaults of Australian Aboriginal crania from southern and central Australia. Traditionally Australian Aboriginals, males and females, involved in agressive dispute will use a substantial wooden implement and strike to the head of thir opponent(Meggitt 1962).The injuries that result from this are more common in females than in male. This form of social interaction must have rigorously selected against those individuals with thinner bones in their cranial vaults. To a large degree this may explain the greatly thickened vaults in Australian Aboriginals relative to Europeans and Northern Chines.This may also provide a clue to the factors resulting in the development of marked cranial vault thickness in Homo erectus.
     

Are Homo sapiens nonsupranuchal fossa and neanderthal suprainiac fossa convergent traits?

The autapomorphic status of the Neanderthal suprainiac fossa was recently confirmed. This was a result of a detailed analysis of the internal bone composition in the area of the suprainiac depression on Neanderthal and Homo sapiens specimens. However, while anatomical differences between Neanderthal suprainiac fossa and the depression in the inion region of the occipital bone of fossil and recent Homo sapiens have been discussed in detail, the etiology of these structures has not been resolved. In this article, the hypothesis that the Homo sapiens non-supranuchal fossa and the Neanderthal suprainiac fossa both formed to maintain the optimal shape of the occipital plane (to minimize strain on the posterior cranial vault) is tested. First, the variation in the expression of the fossa above inion in the crania of recent Homo sapiens from European, African, and Australian samples was examined, and the degree of structural similarity between these depressions and the Neanderthal suprainiac fossa was assessed. Next, the relationship between the shape of the occipital squama in the midsagittal plane and two particular features (the degree of the occipital torus development and the occurrence of a depression in the inion region that is not the supranuchal fossa) were analyzed. Based on the results, it is suggested that the Homo sapiens non-supranuchal fossa and Neanderthal suprainiac fossa are convergent traits.     

Msx2 and Twist cooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault

The flat bones of the vertebrate skull vault develop from two migratory mesenchymal cell populations, the cranial neural crest and paraxial mesoderm. At the onset of skull vault development, these mesenchymal cells emigrate from their sites of origin to positions between the ectoderm and the developing cerebral hemispheres. There they combine, proliferate and differentiate along an osteogenic pathway. Anomalies in skull vault development are relatively common in humans. One such anomaly is familial calvarial foramina, persistent unossified areas within the skull vault. Mutations in MSX2 and TWIST are known to cause calvarial foramina in humans. Little is known of the cellular and developmental processes underlying this defect. Neither is it known whether MSX2 and TWIST function in the same or distinct pathways. We trace the origin of the calvarial foramen defect in Msx2 mutant mice to a group of skeletogenic mesenchyme cells that compose the frontal bone rudiment. We show that this cell population is reduced not because of apoptosis or deficient migration of neural crest-derived precursor cells, but because of defects in its differentiation and proliferation. We demonstrate, in addition, that heterozygous loss of Twist function causes a foramen in the skull vault similar to that caused by loss of Msx2 function. Both the quantity and proliferation of the frontal bone skeletogenic mesenchyme are reduced in Msx2-Twist double mutants compared with individual mutants. Thus Msx2 and Twist cooperate in the control of the differentiation and proliferation of skeletogenic mesenchyme. Molecular epistasis analysis suggests that Msx2 and Twist do not act in tandem to control osteoblast differentiation, but function at the same epistatic level.     

A Collision Probability Model of Portal Vein Tumor Thrombus Formation in Hepatocellular Carcinoma

Hepatocellular carcinoma is one of the most common malignancies worldwide, with a high risk of portal vein tumor thrombus (PVTT). Some promising results have been achieved for venous metastases of hepatocellular carcinoma; however, the etiology of PVTT is largely unknown, and it is unclear why the incidence of PVTT is not proportional to its distance from the carcinoma. We attempted to address this issue using physical concepts and mathematical tools. Finally, we discuss the relationship between the probability of a collision event and the microenvironment of the PVTT. Our formulae suggest that the collision probability can alter the tumor microenvironment by increasing the number of tumor cells.     

Chromosomal fragile site expression in lymphocytes from patients with schizophrenia

Schizophrenia is a common complex mental disorder. The lifetime prevalence of this disease is about 1% across different populations. The etiology is still unknown despite decades of intensive study. This report is aimed at studying the relationship between chromosomal fragile sites and the etiology of schizophrenia. Lymphocytes of 72 schizophrenic patients and 66 healthy controls were cultured in M medium, which is deficient in folic acid, and in medium RPMI1640 with distamycin A. G-banding was carried out on 100 metaphases of each individual. Fragile sites were characterized as specific chromosomal bands that exhibit nonrandom gaps or breaks. Culture in M medium resulted in significant differences in the total number of chromosomal lesions and the total number of cells with chromosomal lesions between patients and controls (P<0.001), while no difference was noted after exposure to distamycin A. In the case of M medium, 17 bands in both patients and controls were recognized as expressing fragile sites nonrandomly using a statistical method based on the relationship of the binomial and F distributions. Further analysis using Fisher’s exact test revealed a significant excess of expression of a rare fragile site at 2q11.2 among patients compared with controls (P<0.05). In the case of distamycin A induction, 13 bands were identified as having nonrandom expression of fragile sites using the same statistical method. A significant excess expression of a fragile site at 9q12 was identified among patients compared with controls by applying Fisher’s exact test (P<0.001). Thus, our data suggest that chromosomal bands 2q11.2 and 9q12 are interesting regions that may harbor important genes associated with schizophrenia. Received: 21 July 1998 / Accepted: 19 September 1998     

Comparing gene expression profiles of Kashin-Beck and Keshan diseases occurring within the same endemic areas of China

In this study, differentially expressed genes in peripheral blood from patients with Kashin-Beck disease and Keshan disease were compared to further investigate the etiology and pathogenesis of both diseases, which occur in a common endemic area of China. Twenty Kashin-Beck disease patients and 12 healthy controls, and 16 Keshan disease patients and 16 healthy controls, were grouped into four pairs. Patients and controls were selected from common endemic areas for the two diseases. Total RNA was isolated from peripheral blood mononuclear cells from all patients and controls, and gene expression profiles analyzed by oligonucleotide microarrays. Sixteen genes differentially expressed in both Kashin-Beck disease and Keshan disease (versus controls) were identified, and comprised nine genes showing synchronous and seven asynchronous expression. The Comparative Toxicogenomics Database shows that expression and biological function of these genes can be affected by multiple environmental factors, including mycotoxin and selenium content, potential environmental risk factors for the two diseases. Thus, these shared differentially expressed genes may contribute to the distinct organ lesions, caused by common environmental risk factors of Kashin-Beck disease and Keshan disease.     

Rhinoplasty: personal evolution and milestones

Over the past 35 years, aesthetic rhinoplasty has evolved from a generic, reductive operation to a highly individualized, problem-specific operation that often combines augmentation with reduction. The author's experience has been marked by the following conceptual and technical milestones that have contributed to an ongoing exploration and advancement of nasal surgery: (1) vestibular stenosis: diagnosis of a surgical consequence; (2) etiology and treatment of supratip deformity: the dynamic relationship of soft-tissue contour to skeleton; (3) etiology and treatment of the tip with inadequate projection: tip graft design; (4) practical aesthetics of balance: the augmentation-reduction approach to rhinoplasty; (5) support of the middle vault: functional and aesthetic effects; (6) malposition of the lateral crura: recognition and management; and (7) the significance of the middle crura: clinical and aesthetic considerations.     

Vaginal vault smears –''know more – do less'': a questionnaire survey of primary health care practitioners

BACKGROUND: The vaginal vault smear is a test for cellular atypia in women who have undergone a hysterectomy. In asymptomatic women the test has poor sensitivity and specificity. Current guidelines recommend: vault smears should not be used after hysterectomy for benign pathology; two vault smears (6 and 12 months postsurgery) should be taken when there is evidence of completely excised CIN II/III in the specimen. AIM: To describe primary health care professionals' self-reported knowledge and behaviour relating to the use of vault smears. DESIGN OF STUDY: Questionnaire. SETTING: South Birmingham. METHODS: Postal questionnaire survey to primary health care professionals (general practitioners and practice nurses, n = 424). Results: Response rate 80.0%, completed response rate 68.9%. Mean knowledge score was 7.3 out of possible 12 (SD 1.9); range 0-10. No significant differences were observed between GPs and practice nurses in knowledge scores, although differences were noted in the frequency of performing vault smears. An inverse relationship was observed between frequency of performing vault smears and level of knowledge about the test. There was a positive association between requesting further information and the 'knowledge score'. Only 11% correctly answered a question based on current guidelines. CONCLUSIONS: Knowledge of current guidelines was poor. Those who undertook fewest vault smears appeared best informed. This suggests that if all primary care professionals practised according to current guidelines, the number of vault smears performed may be reduced. Unnecessary vault smears may cause additional anxiety in women and have financial consequences for the NHS.     

Health and disease at a South Carolina plantation: 1840-1870

The analysis of 36 human skeletons (eight subadults, 13 males, 15 females) recovered during a cemetery relocation near Charleston, SC, provides data on health and disease for a 19th-century sample of Afro-Americans. The majority of the burials date from 1840-1870. Skeletal analysis verified some historical interpretations. Gender differential in mortality is evident with average age at death for males 35 and females 40 years. Females, besides living longer, had more missing and carious teeth but fewer abscesses. Both genders expressed childhood metabolic stress as indicated by linear enamel hypoplasias. Males, however, had a higher incidence (92%) than did females (70%). Age at occurrence was more widely distributed for females, but ages 2-4 were most critical for both genders. Postcranial indications of recovery from acute stress, Harris lines, occurred more frequently for males (45%) than for females (18%). Anemia, probably both genetic and acquired, was a significant health problem for both genders. Cribra orbitalia appeared in 35% of the adult crania, and 80% of the subadults had orbital lesions. Diplotic expansion of the cranial vault and infection were relatively common in the sample. Skeletal reaction to infections appeared in 69% of the males, 60% of the females, and 80% of the subadults. Skeletal changes associated with demanding physical labor were ubiquitous. The shoulder and hip were especially affected by degenerative changes, the cervical vertebrae frequently expressed osteophytosis, and males show a preponderance of Schmorl herniations and hypertrophy of the ulnar supinator crest. Skeletal trace elements indicate a relatively high exposure to lead, strontium concentrations indicative of a diet high in plant foods, and relatively low zinc and copper concentrations.     

The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle

Vaults and telomerase are ribonucleoprotein (RNP) particles that share a common protein subunit, TEP1. Although its role in either complex has not yet been defined, TEP1 has been shown to interact with the mouse telomerase RNA and with several of the human vault RNAs in a yeast three-hybrid assay. An mTep1(-/-) mouse was previously generated which resulted in no apparent change in telomere length or telomerase activity in six generations of mTep1-deficient mice. Here we show that the levels of the telomerase RNA and its association with the telomerase RNP are also unaffected in mTep1(-/-) mice. Although vaults purified from the livers of mTep1(-/-) mice appear structurally intact by both negative stain and cryoelectron microscopy, three-dimensional reconstruction of the mTep1(-/-) vault revealed less density in the cap than previously observed for the intact rat vault. Furthermore, the absence of TEP1 completely disrupted the stable association of the vault RNA with the purified vault particle and also resulted in a decrease in the levels and stability of the vault RNA. Therefore, we have uncovered a novel role for TEP1 in vivo as an integral vault protein important for the stabilization and recruitment of the vault RNA to the vault particle.