The girl from the church of the sacrament: a case of congenital syphilis in XVIII century Lisbon

Syphilis is a sexually or congenitally transmitted infectious disease with an impact on the health of human populations that has undergone important cycles in different countries and periods of history. Its presence was first diagnosed in Europe in the late XIV century. In Portugal, although there are various written records of the infection in the last centuries, there are rare references to it in archeological findings (mummified bodies are also rare in Portugal). The current study describes a probable case of congenital syphilis in an 18-month-old girl buried in the Church of the Sacrament in Lisbon. Her body, dating to the XVIII century, was found mummified together with dozens of others, still not studied. Symmetrical periostitis of the long bones, osteitis, metaphyseal lesions, left knee articular, and epiphyseal destruction, and a rarefied lesion with a radiological appearance compatible with Wimberger's sign all point to a diagnosis of congenital syphilis. The diagnosis of this severe form of the infection, possibly related to the cause of death in this upper-class girl, calls attention to the disease's presence in XVIII century Lisbon and is consistent with the intense mobilization at the time in relation to the risks posed by so-called heredosyphilis. It is the first case of congenital syphilis in a child reported in archeological findings in Portugal, and can be correlated with other cases in skeletons of adults buried in cemeteries in Lisbon (in the XVI to XVIII centuries) and Coimbra (XIX century). Finally, this finding highlights the need to study the entire series of mummified bodies in the Church of the Sacrament in order to compare the paleopathological findings and existing historical documents on syphilis, so as to expand the paleoepidemiological knowledge of this infection in XVIII century Lisbon.     

Subadult health and disease in prehistoric Tonga, Polynesia

This article focuses on the differential diagnosis of pathologic lesions recorded on the limbs and crania of 17 subadults from two pre-European burial mounds in Tonga, western Polynesia. All affected subadults were between the ages of 6 months and 3 years at death. The lesions described consist primarily of subperiosteal new bone deposition on the limbs and endocranial surface. However, the presence of cribra orbitalia in a number of individuals indicates concurrent iron-deficiency anaemia. A differential diagnosis of haematogenous osteomyelitis, congenital syphilis, yaws, scurvy, hypervitaminosis A, trauma, Caffey's disease, and iron-deficiency anaemia is discussed. It was concluded that the most likely cause for the lesions observed is a synergistic relation between infection (weanling diarrhoea, yaws) and metabolic disease (scurvy and possibly hypervitaminosis A). Trauma is not ruled out as contributing to the development of some pathologic lesions. It is concluded that, in the Pacific Islands at least, multiple causes for skeletal pathology in subadults should be considered rather than a single aetiology.     

肝硬化患者术后感染的危险因素及干预措施

目的:感染是肝硬化患者肝移植术后常见的并发症之一,影响患者的治疗效果和生存质量。本文针对肝硬化患者术后感染的危险因素进行分析,探讨有效的干预措施以提高临床疗效,为肝硬化术后并发症的预防提供可借鉴的方法。方法:对2008年10月-2013年9月在我院接受手术治疗的120例肝硬化患者的临床资料进行回顾性分析。根据术后并发症的发生情况选择其中60例发生感染的患者作为感染组,另外60例未发生感染的患者作为对照组。观察两组患者的年龄、肝硬化分期及用药情况等,对比不同的干预措施产生的临床效果。结果:感染组患者的平均年龄、肝功能障碍、抗生素使用量及术前合并感染的比率均显著高于正常对照组,差异具有统计学意义(P0.05)。两组患者进行针对性的护理干预均获得良好的治疗效果,未发生死亡病例。结论:患者的年龄、肝功能分级、用药及合并症等均为肝硬化术后感染的危险因素,临床中应实施针对性的干预措施以提高疗效。     

CIRRHOSIS MORTALITY IN CALIFORNIA—A TREND

The recorded California death experience attributable to cirrhosis of the liver for the period 1910-1957 was collected and analyzed. The analysis clearly demonstrated a progressive increase in age-adjusted death rates for the past thirty-five years, paralleled by a constantly decreasing average age at death. Increasingly, California citizens are dying of cirrhosis of the liver at younger ages.At a time when diagnosis and treatment of cirrhosis of the liver are at their highest points of clinical interest and concern, this analysis suggests that other morbid forces are at work in the production of liver cirrhosis that must be ferreted out by clinicians and epidemiologists.     

性病梅毒的古病理学研究回顾

在抗生素诞生以前的历史时期,密螺旋体属疾病蔓延于新旧大陆,是继免疫缺陷综合症之前人类无法治愈的性传染疾病。密螺旋体类疾病可分为：性病梅毒、地方性梅毒、雅司病、品他病4种。除品他外的3种疾病均会使骨骼发生特异性感染,最终造成骨骼形态上的特殊改变,其中以梅毒所造成的影响最为显著。考虑到目前国内尚未有学者对性病梅毒所引起的骨变异进行研究,本文通过梳理国外关于梅毒的古病理学研究成果,对性病梅毒的鉴定标准及起源等问题进行阐述。     

Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥ 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection.     

Early Medical Skull Surgery for Treatment of Post-Traumatic Osteomyelitis 5,000 Years Ago

Here we describe the findings of a unique example of the early techniques adopted in neurosurgery around 5000 years ago, consisting in a double well healed skull trephination associated with a post-cranial traumatic event occurring intra vitam to a young male from the Early Chalcolithic cemetery of Pontecagnano (South Italy, ca. 4,900 - 4,500 cal BP). Morphological, X-ray and 3D-CT scan skull-cap evaluation revealed that the main orifice was produced by scraping, obtained by clockwise rotary motion of a right-handed surgeon facing the patient, while the partial trephination was carried out by using a stone point as a drilling tool. In both cases, bone regrowth is indicative of the individual''s prolonged postoperative survival and his near-complete recovery. The right femur shows a poorly healed mid-shaft fracture presumably induced by a high energy injury, and a resulting chronic osteomyelitis, affecting both femurs by hematogenous spread of the infection. Our observations on the visual and radiological features of skull and femur lesions, along with evidence on the timing of experimental bone regrowth vs. healing of lower limb fractures associated to long-term bone infections now suggest that this young man underwent a double skull trephination in order to alleviate his extremely painful condition induced by chronic osteomyelitis, which is thought to have been the cause of death.     

Blackbuck antelope (Antilope cervicapra), a new host for Psoroptes cuniculi (Acari: Psoroptidae)

Information was requested on the cause of extensive lesions and death of a blackbuck antelope (Antilope cervicapra). Psoroptes cuniculi, the ear mite of domestic rabbits, was identified as the cause of the lesions. Death of the antelope was attributed to a secondary bacterial infection. This is the first report of P. cuniculi on blackbuck antelope. The potential impact of these mites on blackbuck antelope and other exotics in Texas is unknown.     

Hepatic fibrosis and Fasciola hepatica infection in cattle

This study focuses on the development of fibrosis of the liver of cattle with Fasciola hepatica infection, correlating with the intensity of infection. Animals with an established diagnosis of chronic F. hepatica infection were identified in a slaughterhouse in Lima, Peru. The study included 24 fresh cattle livers from infected animals and two uninfected controls. Tissues were stored at 4 degrees C for approximately 8 h after which they were brought to a necropsy room and examined. Between 9 and 12 biopsies were randomly obtained from each liver. Histological staining of formalin-fixed liver sections with haematoxylin and eosin (H & E) and Masson's trichrome were performed. Liver samples were examined using a pathology protocol that included 30 items. Histopathologically, 16 out of 30 liver specimens (67.6%) showed diffuse fibrotic lesions (cirrhosis) with a mean number of Fasciola of 116 +/- 30 (range 4-435). Pathological data were matched to number of adult parasites and presence of cirrhosis after being reviewed by two independent pathologists. There was concordance between the two pathologists (K = 0.72). The group with cirrhosis showed an average of 116 +/- 30 adult parasites whereas the group not showing cirrhosis contained 56 +/- 28 flukes (P = 0.2). To measure how number of flukes and diagnosis of cirrhosis are related we used Kendall's tau-b coefficient; the correlation was +0.296 (P = 0.04). Receiver Operating Characteristic (ROC) curve results showed that the best point was 38 parasite adults, which had 93.8% sensitivity and 75% specificity. We conclude that as the number of F. hepatica adult forms increases, the likelihood of developing liver fibrosis will also increase in cattle.     

Hepatic injury after whole-liver irradiation in the rat

Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD50/30 day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [131I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract, which increase the host resistance to infection and endotoxemia, resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. The combination of these treatments resulted in additive effects leading to 38% survival at 100 days. These treatments did not, however, prevent the eventual development of radiation-induced liver pathology. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers.     

Social epidemiology of chronic liver disease and cirrhosis mortality in the United States, 1935-1997: trends and differentials by ethnicity, socioeconomic status, and alcohol consumption

This study examines trends and ethnic and socioeconomic differentials in chronic liver disease and cirrhosis mortality in the United States. Age-adjusted death rates from the National Vital Statistics System were used to analyze race and sex-specific mortality trends from 1968 through 1997. Age-adjusted liver cirrhosis mortality and per capita alcohol consumption data from 1935 through 1996 were modeled using time-series regression. Moreover, the Cox hazards regression was applied to the National Longitudinal Mortality Study, 1979-1989, to examine socioeconomic differentials at the individual level, whereas multivariate ordinary least squares regression was used to model state-specific cirrhosis mortality from 1990 to 1992 as a function of socioeconomic variables and alcohol consumption at the ecological level. Chronic liver disease and cirrhosis continues to be an important cause of death in the United States, even after three decades of consistently declining mortality rates. For both men and women aged 25 years and older, significant mortality differentials were found by age, race/ethnicity, marital status, family income, and employment status. For men, marked differentials were also found by nativity, rural-urban residence, and education. Unemployment, minority concentration, and alcohol consumption were major predictors of state-specific cirrhosis mortality. Both time-series and cross-sectional data indicate a strong correlation between alcohol consumption and US cirrhosis mortality. Substantial ethnic and socioeconomic differences in cirrhosis mortality suggest the need for social and public health policies and interventions that target such high-risk groups as American Indians, Hispanic Americans, the socially isolated, and the poor.     

慢性病毒性肝炎研究进展

近年,慢性病毒性肝炎研究领域有较大进展,慢性乙型肝炎病毒（HBV）感染,虽然有了应用广泛、历史较久、且效果较好的疫苗,但迄今仍是世界范围肝硬化和肝癌的主要诱因。传染途径可经产道、性接触和非肠道途径（包括静脉吸毒、血制品等）。成年病人有少有变慢性,但一岁以下患儿90％变成慢性肝炎。慢性肝损伤的临床表现可以是轻微的炎症重到晚期肝硬化,程度不等。α干扰素（IFNα）是治疗活动性肝炎的产宰药物,单核苷酸类药物（lamivudine和adefovir）也具有同样的疗效。晚期肝病和肝癌患者可进行移植,但异常伴发移植物的感染。乙型肝炎免疫球蛋白和新型抗病毒药物联合应用,可降低移植物感染的严重性。丙型肝炎病毒（HCV）在20世纪后期感染了大约1％的世界人口。这中RNA病毒非经口传播,绝大多数病人变成慢性肝炎,约20％逐渐演变成肝硬化或肝癌。用IFNα和病毒唑（Ribavirin）联合治疗,约40％病人的病理表现有所改善。肝移植对某些病例是适宜的,但移植物感染仍是悬而未决的问题,新发现的庚型肝炎病毒（HGV）和TT病毒目前认为并不引起严重的肝损害。     

Trend of mortality observed in a cohort of drug addicts of the metropolitan area of Bologna, North-Eastern Italy, during a 25-year-period

The aim of our study is to evaluate the temporal trend of deaths in a cohort of i.v. drug users (IVDU) followed in a city of Northen Italy (Bologna), and to assess its relationship with HIV infection and AIDS, and availability of potent anti-retroviral therapy. One thousand and 214 IVDUs (mainly heroin addicts), 916 males and 298 females, attending an out-patient service for treatment and prevention of substance abuse between 1977 and November 1996, were enrolled into our observational cohort, and their vital status was ascertained up to December 31, 2002. The large majority of enrolled subjects were born in the Bologna metropolitan area and surroundings; no extra-European immigrants were present. During the observation period, 271 IVDUs (22.3%) died, 211 males (23.0%), and 60 females (20.1%). No death was recorded before 1984. Main death causes result as follows: AIDS (52.8% of episodes), heroin overdose (22.1%), street accidents (7.4%), decompensated liver cirrhosis (6.3%), and suicide (2.9%). The highest absolute number of deaths was observed between years 1991 and 1996. Crude mortality rate caused by AIDS was 10.0 per 1000 for males and 13.2/1000 for females; the rate of death due to other causes proved 11.1/1000 among males and 5.2/1000 among females. In most recent years, a sharp decrease in the number of AIDS-related deaths, attributable to the increased use of potent antiretroviral regimens, was recorded among IVDUs, although overall mortality rate remained appreciable.     

Contribution of human data to the analysis of human carcinogenesis

Human data strongly suggest that small doses or low concentrations of genotoxic agents cause only a relatively small number of human cancers. They emphasize the role of promotion, in particular that associated with cell proliferation. There is therefore a qualitative difference between high doses of genotoxic agents which provoke cell death and a compensatory increase in cell division, and low doses which do not. During the promotion phase, human data demonstrate the importance of induced genetic instability and defects in apoptosis as well as that of cell immortalization which play a main role for the accumulation in a cell genome of several specific lesions. Carcinogenesis is a complex process in which initial mutations do not appear to be a limiting or crucial step. This view is supported by the paramount influence of age on the induction by radiation of thyroid and breast cancer. It is also compatible with practical thresholds observed in subjects whose bones or liver were exposed to alpha-emitters, as well as with the curvilinearity in the leukemia incidence dose-response in the Japanese atomic bomb survivors. The linear no threshold model assumes that: 1) the probability of DNA lesion repair is constant whatever the dose and, hence, the number of lesions provoked in the same cell and the surrounding cells; 2) the probability for a damaged cell to evolve toward an invasive cancer is not influenced by the possible promotional effect of further irradiation or induced tissue proliferation, nor the control exerted by surrounding cells. These assumptions deserve a critical analysis.     

Immunohistochemical assessment of proliferating cell nuclear antigen in primary hepatocellular carcinoma and dysplastic nodules

A complementary way for the assessment of HCC prognosis is represented by the analysis of molecular markers. Thus, immunohistochemical assessment of proliferation can describe tumor aggressiveness, probability of local recurrence or metastasis potential, being very useful for the assessment of recurrence-free survival and survival until death. The aim of our study was to assess proliferating cell nuclear antigen activity in HCC and dysplastic nodules as compared with surrounding nonneoplasic areas. Immunohistochemical techniques were thus performed on the samples obtained by ultrasound-guided liver biopsies or intraoperative biopsies, in 32 patients with HCC, as well as in 3 patients with dysplastic nodules ocurring in liver cirrhosis. Expression of PCNA within extranodular areas of the HCC patients in the absence or presence of cirrhosis, was increasing from 40% to 70%, respectively. PCNA expression further increased within intranodular areas of dysplastic nodules and HCC, to 100% and 96.88%, respectively. A progressive increase of the mean values of PCNA-LI was also observed from extranodular areas without or with cirrhosis, towards intranodular areas of dysplastic nodules and HCC (4.2%, 6.8%, 31.9%, respectively). Dysplastic nodules can thus be considered lesions with a high-proliferation rate, representing an early stage of hepatocarcinogenesis. This supported the current recommendations for borderline hepatocellular nodules identified by ultrasound, which indicate an aggressive treatment similar to malignant lesions. In summary, we demonstrated a progressively increasing rate of cellular proliferation, from extranodular non-neoplasic areas to intranodular areas (dysplastic nodules and HCC), as reflected by an increased expression of proliferating cell nuclear antigen labelling index.     

Mechanisms of Pathogenesis in Listeria monocytogenes Infection II. Characterization of Listeriosis in the CD-1 Mouse and Survey of Biochemical Lesions

Several physiological and biochemical changes which occur in CD-1 pathogen-free mice during the course of infection with Listeria monocytogenes strain A4413 have been examined. Mice injected with 10(4) to 10(6) organisms by the intraperitoneal route displayed a significant depression in weight gain. In contrast, at 24 hr after infection an increment in total liver weight averaging 0.1 g was observed. The ratios of liver to body weight increased throughout the observation period. As the severity of the infection increased, food intake, as well as total liver protein and nitrogen, showed a corresponding decrease, with the diminution being most evident immediately prior to the death of the animals. Blood urea nitrogen remained relatively constant for 24 hr and then increased continuously as the infection progressed to the acute stage. Total liver lipid increased until the death of the animals. At 72 hr postinfection, a significant decrease in oxidative phosphorylation was observed. Xanthine dehydrogenase activity increased, with maximal values obtained 72 hr after infection. Uric acid levels remained constant for 24 hr, diminished at 48 hr, and then increased until the death of the animals. After 24 hr, uricase activity showed a slight increase. This activity returned to within normal ranges at 48 hr and decreased as the infection progressed to the acute stage at 72 hr. The results support the hypothesis that at least a part of the cause of death is a derangement in hepatic purine and carbohydrate metabolism. The data are also consistent with the possibility of changes in iron transport in the infected mice.     

Inhibition of cytochrome c release in Fas-mediated signaling pathway in transgenic mice induced to express hepatitis C viral proteins

Persistent hepatitis C virus (HCV) infection often progresses to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Numerous viruses have been reported to escape from apoptotic mechanism to maintain persistent infection. In the present study, we characterized the effect of HCV proteins on the Fas signal using HCV transgenic mice, which expressed core, E1, E2, and NS2 proteins, regulated by the Cre/loxP switching system. The transgene expression of HCV transgenic mice caused resistance to Fas antibody stimulated lethality. Apoptotic cell death in the liver of HCV protein expressing mice was significantly reduced compared with nonexpressing mice. Histopathological analysis and DNA fragmentation analysis revealed that the HCV proteins suppressed Fas-mediated apoptotic cell death. To identify the target pathway of HCV proteins, we characterized caspase activity. The activation of caspase-9 and -3/7 but not caspase-8 was inhibited by HCV proteins. Cytochrome c release from mitochondria was inhibited in HCV protein expressing mice. These results indicated that the expression of HCV proteins may directly or indirectly inhibit Fas-mediated apoptosis and death in mice by repressing the release of cytochrome c from mitochondria, thereby suppressing caspase-9 and -3/7 activation. These results suggest that HCV may cause persistent infection, as a result of suppression of Fas-mediated cell death.     

Pathological changes in the liver of a senescence accelerated mouse strain (SAMP8): a mouse model for the study of liver diseases

Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1). The livers of SAMP8 mice show fatty degeneration, hepatocyte death, fibrosis, cirrhotic changes, inflammatory mononuclear cell infiltration and sporadic neoplastic changes. SAMP8 mice also show abnormal liver function tests: significantly increased levels of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Furthermore, titers of murine leukemia virus are higher in livers of SAMP8 than in those of SAMR1 mice. Our observations suggest that SAMP8 mouse strain is a valuable animal model for the study of liver diseases. The possible mechanisms of liver damage in SAMP8 mice are also discussed.     

Experimental infection of wild‐caught European rabbits (Oryctolagus cuniculus) with Sarcoptes scabiei from a naturally infected wild rabbit

Scabies was recently reported for the first time in the European wild rabbit, Oryctolagus cuniculus (Lagomorpha: Leporidae). We experimentally exposed 10 seronegative wild‐caught rabbits to skin from a mangy wild rabbit. Serological, physiological, parasitological and histopathological changes were recorded. Three rabbits developed antibodies at 2–5 weeks post‐infection (w.p.i.), two of which then developed lesions at 7 w.p.i. One of these had a small area of alopecia on the hind limb that healed naturally within 1 week; the other developed more extensive lesions restricted to the hind limbs (as typically observed in wild rabbits) that lasted until the rabbit died (12.5 w.p.i.). The third rabbit died of trauma 5 w.p.i. before developing any lesions. Antibodies in the healed rabbit disappeared from serum at 8 w.p.i., whereas antibody levels in the sick rabbit increased until its death. Disseminated intravascular coagulation and hepatic necrosis, probably arising from a concomitant infection with rabbit haemorrhagic disease virus, were the likely final cause of death in this rabbit. The mangy rabbit that served as a donor died of a multifocal fibrinosuppurative pneumonia that may have been secondary to the skin bacterial pyoderma.