Syphilitic Aortitis: Autopsy Experience at the Ottawa General Hospital Since 1950

Twenty-six cases of syphilitic aortitis were found among 4173 autopsies performed at the Ottawa General Hospital since 1950. Although 10 aortic aneurysms, nine instances of coronary ostial stenosis and five examples of aortic incompetence were present in 20 cases, a clinical diagnosis of syphilitic aortitis had been established in only two patients. It is paradoxical that the clinical diagnosis of syphilitic aortitis is becoming less accurate as surgical techniques for the correction of its complications are being constantly improved.     

Skeletal manifestations of hypothyroidism from Switzerland

Hypothyroidism is caused by a deficiency in the synthesis of thyroid hormone. Dwarfism is the most obvious skeletal manifestation, but most people with hypothyroidism do not have any skeletal evidence of the disease. When the skeleton is affected, the severity of this manifestation depends on the degree of the deficiency and age of onset. Endemic hypothyroidism typically is linked to specific ecological settings such as the high mountains where iodine is absent, or else it occurs with very low concentrations in water and soil. In these areas, the prevalence may be as high as 8%. The disease can be expected to occur in archaeological human skeletal samples from endemic regions. Sporadic hypothyroidism is caused by a deficiency in the thyroid gland itself, and is not linked to any specific environmental context. The disease may be the result of a genetic defect, but can also be caused by other pathological conditions that may affect the thyroid gland, including infection and cancer. The skeletal abnormalities of the two variants will be indistinguishable in archaeological human remains. In order to identify hypothyroidism in archaeological skeletal samples, one must be aware of the differences in pathological skeletal changes seen in hypothyroidism in comparison with other diseases, such as achondroplasia, that can cause similar abnormalities. Twelve clinically documented cases of hypothyroidism provide data for understanding the skeletal abnormalities associated with this disease. All 12 are modern documented cases from Switzerland, where endemic hypothyroidism occurred in the iodine-deficient Alpine regions. However, at least one case in the sample was caused by a defect in the thyroid gland itself.     

Skeletal Lesions in Human Tuberculosis May Sometimes Heal: An Aid to Palaeopathological Diagnoses

In three to five percent of active cases of tuberculosis, skeletal lesions develop. Typically, these occur on the vertebrae and are destructive in nature. In this paper, we examined cases of skeletal tuberculosis from a skeletal collection (Galler Collection) with focus on the manifestation of bony changes due to tuberculosis in various body regions in association with antibiotic introduction. This skeletal collection was created in 1925–1977 by a pathologist at the University Hospital in Zürich, Ernst Galler. It includes the remains of 2426 individuals with documented clinical histories as well as autopsies. It contained 29 cases of skeletal tuberculosis lesions. We observed natural healing of vertebral lesions through several processes including fusion of vertebrae, bone deposition and fusion of posterior elements. In these cases, we observed a higher frequency and proportion of bone deposition and fusion of posterior vertebral elements where pharmacological agents were used. There were also four cases of artificial healing through surgically induced posterior spinal fusion. With the introduction of pharmaceutical treatments, the number of individuals with multiple tuberculous foci decreased from 80% to 25% when compared to individuals who did not receive any drug therapy. Investigation of comorbidities showed that pneumonia, pleuritis and being underweight were consistently present, even with pharmaceutical treatment. Our results have applications in palaeopathological diagnoses where healing and consequent bone deposition may complicate differential diagnoses.     

Calcium binding of arterial tropomyosin: involvement in the thin filament regulation of smooth muscle

Bovine aortic tropomyosin has been isolated by DEAE-Sepharose chromatography following isoelectric precipitation and ammonium sulfate fractionation. A single polypeptide [Mr 36 000 on a sodium dodecyl sulfate (SDS)-polyacrylamide gel] was obtained under different electrophoretic conditions. The amino acid composition of bovine tropomyosin was very similar to that of rabbit skeletal muscle; the amino-terminal residue is blocked. The molecular weight of the native tropomyosin (76 000), which is twice that calculated from the SDS-polyacrylamide gel, suggests that the molecule is a dimer. The diffusion coefficient of 3.4 X 10(-7) cm2 s-1 and the frictional coefficient of 1.7 indicate that the molecule is asymmetric. Comparative high-pressure liquid chromatography peptide mapping of rabbit skeletal and bovine aortic tropomyosins shows primary structure variation. Bovine aortic tropomyosin binds calcium under physiological conditions of pH and ionic strength (22 mol of Ca2+/mol of tropomyosin with a Kd of 1.4 mM). Such a property is not shared by skeletal tropomyosin. In low Mg2+ concentration, both skeletal and aortic actin activations of the skeletal myosin ATPase activity are calcium independent. Addition of aortic tropomyosin to a hybrid actomyosin (aortic actin, skeletal myosin) yields an enhancement of the actin activation of the myosin ATPase activity, but the addition of skeletal tropomyosin yields a decrease of this activity. However, both the enhancement and decrease are calcium dependent. Addition of skeletal or aortic tropomyosin to an actomyosin system, where both actin and myosin come from skeletal muscle, yields only an enhancement of the actin activation of the myosin ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Natural variation and differential diagnosis of skeletal changes in tuberculosis

Twenty-six documented cases (17 blacks, 9 whites) of skeletal tuberculosis from the Hamann-Todd Osteological Collection, Cleveland Museum of Natural History, were analyzed for lesion variability and patterns of multiple site involvement. In addition, several documented cases of pathologic conditions (osteomyelitis, vertebral fractures, and malignant bone tumors) that resemble skeletal tuberculosis were photographed and described for use in differential diagnosis. The range of variation of tuberculous lesions was found to be considerable. Thirty-eight percent (10/26) of the cases display skeletal lesions in two or more regions concomitantly. The average number of vertebrae affected, as well as the incidence of multiple bone involvement, were found to be higher in blacks. Certain combinations of skeletal lesions (e. g., spine-rib, spine-rib-sternum, and spine-hip) may be useful in the diagnosis of tuberculosis in dry bone material.     

Skeletal manifestations of rickets in infants and young children in a historic population from England

Gross and radiographic changes characteristic of inadequate bone mineralization due to rickets are described in 21 immature skeletons from a 19th century urban population from Birmingham, England. The aims of the study are as follows: to evaluate and if possible augment existing dry-bone criteria for the recognition of rickets in immature skeletal remains; to investigate the value of radiography for the paleopathological diagnosis of rickets; and to compare and contrast the expression of rickets in this group with that previously documented for a rural agrarian population from Wharram Percy, England. Some gross skeletal signs of rickets which were not previously well-documented in paleopathological studies are noted. The worth of radiography for evaluating structural changes to both cortical and trabecular bone in the disease is demonstrated, and features useful for the interpretation of vitamin D deficiency are discussed. The pattern of skeletal elements affected and the severity of changes differs in the Birmingham group from that seen in the comparative rural population. It is emphasized that a variety of factors may influence the expression of rickets in paleopathological material, including rate of skeletal growth, age cohort affected, and intensity of vitamin D deficiency. Nevertheless, careful analysis, not only of the frequency of rickets but also of the degree of severity of lesions and the patterning with respect to skeletal elements affected, may enable more nuanced understanding of the biocultural context of the disease in earlier populations.     

Functional implications of skeletal diversity in two South American tamarins

This study examines the relationship between positional behavior and morphology for two closely related South American tamarin species, Saguinus fuscicollis illigeri and Saguinus oedipus oedipus. Although never systematically documented, the two species are suspected of exhibiting highly similar yet subtly different locomotor behaviors with a greater propensity for climbing, springing, and more powerful leaping in S. oedipus. Fourteen measurements reflecting biomechanical structuring were taken from the postcranial skeleton of 28 individuals of each species. The data were reduced to principal component scores and subjected to a multiple analysis of variance to determine the extent of intergroup skeletal variation. Areas of significant skeletal diversity were interpreted functionally. The results suggest that the differences in functional patterning among the two species is consistent with the behavioral hypothesis. It is concluded that subtle changes in positional behavior may be capable of altering skeletal morphology.     

Adaptations of skeletal muscle grafts to chronic changes of physical activity

After grafting, many structural and functional characteristics of skeletal muscle change with time until reaching a stable value. For several characteristics, these stable values are less than those observed in control skeletal muscle. Characteristics such as mass and fiber cross-sectional area are influenced by chronic changes in physical activity. The extent of our understanding of the dimensions and mechanisms of activity-induced adaptations of grafts is limited and based solely on experiments with rats. Improvements in mass, protein content, oxidative capacity, and glycogen concentration have been documented with conditioning by running of sufficient intensity and duration. The growth and development of soleus muscle grafts are severely impaired when normal weight-bearing activity is removed. The mass and maximum tension development of grafts are increased with ablation of muscles that function synergistically to the grafts, but are diminished after chronic electrical stimulation. Chronic electrical stimulation does increase oxidative capacity, capillarity, and the resistance to fatigue. Much remains to be learned about the mechanisms by which activity-related adaptations occur in skeletal muscle grafts.     

THE VALUE OF ECHOCARDIOGRAPHY IN THE MANAGEMENT OF ACUTE AORTIC INSUFFICIENCY

Three cases of acute rupture of the aortic cusp complicating bacterial endocarditis are described. Special emphasis is placed on the value of serial echocardiography as a means of identifying progressive changes in aortic valve anatomy during the destructive process of the disease. Prior to the results of blood cultures, an echocardiogram confirmed a diagnosis of vegetations on the valve cusps. It also demonstrated flailing of the aortic cusp, which was confirmed at operation. Echocardiographic findings of flailing aortic valves in these patients coincided with the onset of acute aortic insufficiency and contributed to the timing of surgical intervention for replacement of the affected valves.     

Syphilitic infection impairs immunity by inducing both apoptosis and pyroptosis of CD4+ and CD8+ T lymphocytes

Syphilis is an important health problem worldwide; however, few studies have probed the impact of syphilitic infection on T cell turnover. The mechanisms behind the frequency of T cell subset changes and the associations between these subsets during syphilitic infection remain unclear. Herein, we used a cell-staining method and flow cytometry to explore changes in T cell subpopulations and potential contribution of apoptosis and pyroptosis that triggered therein. We investigated caspase-1-mediated pyroptosis and caspase-3-mediated apoptosis of CD4⁺ and CD8⁺ T cells, the major effector lymphocytes with pivotal roles in the pathogenesis of infectious diseases. We found that the levels of caspase-1 and caspase-3 increased in both the circulation and intracellularly in CD4⁺ and CD8⁺ T cells. Caspase-1 showed a continual increase from early latent stage infection through to phase 2 disease, whereas caspase-3 increased through to phase 1 disease but declined during phase 2. In addition, serum levels and intracellular expression of caspase-1 and caspase-3 were positively correlated. Overall, this study increases our understanding of how syphilitic infection influences CD4⁺ and CD8⁺ T-cell turnover, which may help with designing novel and effective strategies to control syphilis infection and prevent its transmission.     

An early Indian cranium from the Medicine Crow site, (39BF2), Buffalo County,South Dakota

Artifacts of Paleoindians have been found in most if not all of the Plains states; however, documented human skeletal remains from this early period are rare. The Medicine Crow cranium dates by stratigraphy and by the amount of absorbed alpha and beta radiation at between 5,000 and 2,000 B.C. This places this young adult male in the Archaic period and represents the earliest documented human skeletal material from South Dakota. It compares favorably in age with other well documented human skeletons from the Plains area, such as Lansing Man (Kansas) (3579 B.C.). Metrically, (with a cranial index of 76.7) and morphologically the Medicine Crow cranium falls well within the range of other early or middle Archaic skeletons.     

Physical properties of myosin from aortic smooth muscle.

Porcine aortic myosin is a smooth muscle contractile protein similar to its striated muscle counterpart. Electrophoresis in sodium dodecyl sulfate indicates that the molecule consists of three classes of subunits with polypeptide chain molecular weights of 192,000, 19,000, and 15,000. At 277 nm the absorption spectrum gives an extinction coefficient for aortic myosin of 0.558 cm2/mg; the circular dichroism spectrum of the protein indicates that aortic myosin contains about 70% of its residues in the alpha-helical configuration. Amino acid analysis shows that the smooth muscle myosin has significantly more arginine and leucine and significantly less valine and isoleucine than rabbit skeletal muscle myosin. Other studies yielded these data: Vapp = 0.716 mL/g [eta] = 0.213 mL/mg, S20, w = 5.84 x 10(-13)S. Similar studies with rabbit skeletal muscle myosin indicate that Vapp = 0.711 mL/g and S20, w = 6.36 x 10(-13)S. These properties suggest that aortic myosin, like skeletal muscle myosin, behaves hydrodynamically like a rigid rod.     

Role of myokines in exercise and metabolism.

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an "exercise factor," which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as "myokines." Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named "myokines." Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.     

Vagal inhibitory effects on peripheral circulation in acute coronary occlusion.

The reflex adjustments of the peripheral circulation in response to acute coronary occlusion were studied in anesthetized dogs with isolated vascular beds perfused at constant flow. Coronary occlusion caused significant increases in perfusion pressure which averaged 27 +/- 4 mmHg in the hindlimb, 19 +/- 8 mmHg in skeletal muscle, and 13 + 5 mmHg in the mesenteric artery. These responses were less than half those caused by a similar decrease in aortic pressure obtained with hemorrhage. Coronary occlusion caused no significant changes in renal and paw circulations, while marked vasoconstriction resulted from hemorrhage. When aortic pressure was maintained constant throughout the duration of coronary occlusion, there was a significant vasodilatation in all beds studied. After vagotomy, coronary occlusion caused a constrictor response similar in magnitude to that caused by hemorrhage in each vascular bed and the dilator responses to occlusion at constant aortic pressure were abolished. Both constrictor and dilator changes were prevented by alpha-adrenergic blockade. Mechanical distension of the left ventricle in four dogs with carotid sinus nerves cut caused a significant reflexdilatation in the hindlimb. Thus, coronary occlusion initiates an inhibitory reflex mediated by vagal afferents which opposes peripheral vasoconstriction most effectively in the renal and paw circulations.     

Critical Transitions in Early Embryonic Aortic Arch Patterning and Hemodynamics

Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a temporal window of increased vulnerability to aberrant aortic arch morphogenesis with the potential for profound effects on subsequent cardiovascular morphogenesis.     

Age determination from dental microstructure in juveniles

The crypts outside St Bride's Church, London, contain a documented collection of skeletal remains dating from the mid-18th century. Some of these remains became mixed during post-war restoration work on the church. The worst example of such mixing involves ten infants that were boxed all together with their corresponding coffin plates. All the infants were aged between 1 and 4 years at death. Recognized skeletal aging criteria proved unsuccessful in identifying the bodies. A more precise method of age estimation was utilized in order to separate these individuals. Age was determined using the incremental markers found in dental microstructure which are thought to be formed in circadian and circaseptan rhythms. The resulting age estimates were compared with the real ages obtained from the coffin plates and death certificates. Confident identification was achieved in eight out of ten cases. This study illustrates the potential value of a little-known aging method in circumstances where commonly used methods have proved unsuccessful. © 1995 Wiley-Liss, Inc.     

Manufactured populations: What do contemporary reference skeletal collections represent? A comparative study using the Maxwell Museum documented collection

The extent to which archaeological or cemetery skeletal collections accurately represent the population from which they were drawn cannot be known. The creation of documented or forensic skeletal collections, derived from donation or autopsy, was intended to overcome many of the problems inherent in archaeological populations, yet it is misleading to assume such collections represent a specific or defined population. This study compares the documented skeletal collection curated at the Maxwell Museum to annual demographic information from three relevant populations: (i) the living population of New Mexico (NM), (ii) the deceased of NM, and (iii) the subset of decedents who undergo a medicolegal death investigation or autopsy. Results indicate that the Maxwell Documented collection differs significantly from all three populations in every variable examined: age, sex, ethnicity/race, cause, and manner of death. Collection development that relies on body donation or retention of unclaimed bodies under coroner/medical examiner statutes results in a biased sample, with significant overrepresentation of males, Whites, the elderly, those who die unnatural deaths and individuals with antemortem traumatic injury or surgical intervention. Equally problematic is the perception that the collection has documented race or ethnicity, when in fact only 17% was self-reported, while the affinity of the remaining individuals was determined by pathologists or other observers. Caution is warranted in how this and similar collections are used and interpreted by researchers. Although documented reference collections are useful in developing methods of estimating age or sex, they are not a proxy for modern or racially/ethnically defined populations.     

A picture of tuberculosis in young Portuguese people in the early 20th century: a multidisciplinary study of the skeletal and historical evidence

The aim of this study was to examine the evidence, and consider the differential diagnosis, for tuberculosis (TB) in juvenile individuals from early 20th century documented skeletons. There are 66 male and female juvenile individuals in the Coimbra Identified Skeletal Collection (CISC) with an age at death ranging from 7-21 years. The individuals died between 1904-1936 in different areas of Coimbra, Portugal. Eighteen of these individuals died from TB affecting different parts of the body. Thirteen (72.2%) showed skeletal lesions that may be related to this infection. Of the 48 individuals with a non-tuberculous cause of death, only 2 (4.2%) had skeletal changes that could be attributed to TB. The distribution of skeletal manifestations caused by the types of TB under study, based on macroscopic and radiological findings, is described and discussed. In addition, the medical records from 6 tuberculous individuals who died in Coimbra University Hospital (CUH) were analysed, and the information, including their diet and access to treatment, is presented. This work, based on data arising before antibiotics became available for treatment, can contribute to the future diagnosis of TB in non-documented skeletal material, and will facilitate a more reliable diagnosis of TB in juvenile individuals.     

The ATPMg-dependent phosphatase is present in mammalian vascular smooth muscle

An ATPMg-dependent phosphorylase phosphatase was identified in vascular smooth muscle from bovine aorta. The smooth muscle enzyme, like the corresponding enzyme from striated muscle, exists as an inactive phosphatase (F_C-enzyme) which can be activated by a protein, F_A, in the presence of ATP and Mg²⁺. Moreover, smooth muscle F_C is activatable by skeletal muscle F_A and skeletal muscle F_C can be activated by smooth muscle F_A. The mode of activation of aortic F_C by aortic F_A is similar to that reported for the skeletal muscle proteins. In accord with earlier findings obtained with the skeletal muscle system, the activity of the aortic phosphatase is inhibited by a specific heat-stable modulator protein (previously called phosphatase inhibitor-2). Thus, the fundamental properties of arterial ATPMg-dependent phosphatase appear to be identical to those of its skeletal muscle counterpart which purportedly represents the major phosphorylase phosphatase in that tissue. Since glycogen phosphorylase is activated when vascular smooth muscle contracts, ATPMg-dependent protein phosphatase may participate in coordinating arterial metabolism and contractility.     

PKA-induced Receptor Activator of NF-κB Ligand (RANKL) Expression in Vascular Cells Mediates Osteoclastogenesis but Not Matrix Calcification

Vascular calcification is a predictor of cardiovascular mortality and is prevalent in patients with atherosclerosis and chronic renal disease. It resembles skeletal osteogenesis, and many bone cells as well as bone-related factors involved in both formation and resorption have been localized in calcified arteries. Previously, we showed that aortic medial cells undergo osteoblastic differentiation and matrix calcification both spontaneously and in response to PKA agonists. The PKA signaling pathway is also involved in regulating bone resorption in skeletal tissue by stimulating osteoblast-production of osteoclast regulating cytokines, including receptor-activator of nuclear κB ligand (RANKL) and interleukins. Therefore, we investigated whether PKA activators regulate osteoclastogenesis in aortic smooth muscle cells (SMC). Treatment of murine SMC with the PKA agonist forskolin stimulated RANKL expression at both mRNA and protein levels. Forskolin also stimulated expression of interleukin-6 but not osteoprotegerin (OPG), an inhibitor of RANKL. Consistent with these results, osteoclastic differentiation was induced when monocytic preosteoclasts (RAW264.7) were cocultured with forskolin-treated aortic SMC. Oxidized phospholipids also slightly induced RANKL expression in T lymphocytes, another potential source of RANKL in the vasculature. Because previous studies have shown that RANKL treatment alone induces matrix calcification of valvular and vascular cells, we next examined whether RANKL mediates forskolin-induced matrix calcification by aortic SMC. RANKL inhibition with OPG had little or no effect on osteoblastic differentiation and matrix calcification of aortic SMC. These findings suggest that, as in skeletal tissues, PKA activation induces bone resorptive factors in the vasculature and that aortic SMC calcification specifically induced by PKA, is not mediated by RANKL.