Impact of HIV infection on mortality in young men in a London health authority.

OBJECTIVE--To determine the number of deaths attributable to HIV infection among men aged 15-64 in a geographically defined population in the United Kingdom. DESIGN--Retrospective review of death certificates and linkage with local and national HIV and AIDS surveillance data. SETTING--Riverside District Health Authority, London. MAIN OUTCOME MEASURES--Numbers of deaths attributed to HIV infection in male residents of Riverside aged 15-64 and 15-44 over a six month period. Proportion of attributed deaths were (i) identified from death certificates by the Office of Population Censuses and Surveys as being due to HIV infection and (ii) reported as cases of AIDS or HIV related deaths to the Public Health Laboratory Service Communicable Disease Surveillance Centre. RESULTS--34 of 213 (16%) deaths in men aged 15-64 and 27 of 69 (39%) deaths in men aged 15-44 were attributed to HIV infection. Six of 33 (18%) attributed deaths were identified by the Office of Population Censuses and Surveys and 32/34 (94%) were reported to the Communicable Disease Surveillance Centre. CONCLUSIONS--HIV infection was the leading cause of death in male residents of Riverside aged 15-44 and the third commonest cause of death in those aged 15-64. Most individuals dying of known HIV infection were reported to the Communicable Disease Surveillance Centre but identification of the true cause of death from the process of death certification was poor. Measures to improve the certification of HIV and AIDS or the use of AIDS surveillance information correctly to code the cause of death needs to be considered to ensure that the true impact of HIV infection is reflected in routine mortality statistics.     

Isolation of a type D retrovirus from B-cell lymphomas of a patient with AIDS.

An atypical syncytial variant of a high-grade Burkitt's-type B-cell lymphoma from a patient with AIDS who was seropositive for human immunodeficiency virus type 1 was studied. A productive type D retrovirus infection was identified in early-passage cell lines derived from two lymphomas from this patient. Nucleotide and amino acid sequence analysis as well as immunologic reactivity indicated that the isolated virus was highly related to Mason-Pfizer monkey virus (MPMV). MPMV is an immunosuppressive type D retrovirus that causes an AIDS-like syndrome in rhesus macaques. Amplification of DNA from the patient's diagnostic bone marrow biopsy specimen by polymerase chain reaction generated the appropriate MPMV-specific fragments and indicated that the patient was infected with the MPMV-like retrovirus. In addition, the patient's serum contained antibodies which recognized type D viral env proteins (gp70 and gp20) and gag proteins (p27 and p14). Although there have been reports of human cell lines infected with type D retroviruses and of type D-reactive human sera, this is the first evidence of a type D retrovirus infection in a human confirmed by virus isolation, serum reactivity, and viral DNA identification in tumor tissue.     

European hares in Chile: a different lagomorph reservoir for Mycobacterium avium subsp. paratuberculosis?

Ruminants are the principal host for infection by Mycobacterium avium subsp. paratuberculosis (Map), the cause of Johne's disease. Based on studies of a Map-infected population of European rabbits (Oryctolagus cuniculus) in Scotland, lagomorphs as a broad taxonomic order were proposed as potential nonruminant reservoirs for Map. To determine whether a different lagomorph species may serve as a wildlife reservoir, we investigated Map infection in European hares (Lepus europaeus) sharing habitat with known Map-infected dairy cattle in southern Chile. Fecal, mesenteric lymph node, and ileal samples were aseptically collected from 385 wild hares for liquid culture and real-time polymerase chain reaction identification of acid-fast isolates. All tissue samples were also acid-fast stained and examined microscopically. We isolated Map from at least one tissue from 48 hares (12.6%) and fecal samples from 16 hares (4.2%). No Map was found in tissues of eight of the fecal-culture-positive hares. Histologically, all tissues from all hares were within normal limits, and no acid-fast organisms were observed in any sample. Active infection, implying amplification of the organism secondary to resultant disease, was not evident. With this report Map isolations on a population versus incidental detection have now been made from two lagomorph species. However, although the rabbit population studied in Scotland appears to function as a Map reservoir, the hares studied in Chile appear to be a dead-end host, serving only as potential mechanical vectors for the organism.     

Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis

Bone destruction is a frequent and clinically serious event in patients with rheumatoid arthritis (RA). Local joint destruction can cause joint instability and often necessitates reconstructive or replacement surgery. Moreover, inflammation-induced systemic bone loss is associated with an increased fracture risk. Bone resorption is a well-controlled process that is dependent on the differentiation of monocytes to bone-resorbing osteoclasts. Infiltrating as well as resident synovial cells, such as T cells, monocytes and synovial fibroblasts, have been identified as sources of osteoclast differentiation signals in RA patients. Pro-inflammatory cytokines are amongst the most important mechanisms driving this process. In particular, macrophage colony-stimulating factor, RANKL, TNF, IL-1 and IL-17 may play dominant roles in the pathogenesis of arthritis-associated bone loss. These cytokines activate different intracellular pathways to initiate osteoclast differentiation. Thus, over the past years several promising targets for the treatment of arthritic bone destruction have been defined.     

Cranial anatomy,taxonomic implications and palaeopathology of an Upper Jurassic Pliosaur (Reptilia: Sauropterygia) from Westbury,Wiltshire, UK

Abstract: Complete skulls of giant marine reptiles of the Late Jurassic are rare, and so the discovery of the 1.8‐m‐long skull of a pliosaur from the Kimmeridge Clay Formation (Kimmeridgian) of Westbury, Wiltshire, UK, is an important find. The specimen shows most of the cranial and mandibular anatomy, as well as a series of pathological conditions. It was previously referred to Pliosaurus brachyspondylus, but it can be referred reliably only to the genus Pliosaurus, because species within the genus are currently in need of review. The new specimen, together with another from the same locality, also referred to P. brachyspondylus, will be crucial in that systematic revision, and it is likely that the genus Pliosaurus will be found to include several genera. The two Westbury Pliosaurus specimens share many features, including the form of the teeth, but marked differences in the snout and parietal crest suggest sexual dimorphism; the present specimen is probably female. The large size of the animal, the extent of sutural fusion and the pathologies suggest this is an ageing individual. An erosive arthrotic condition of the articular glenoids led to prolonged jaw misalignment, generating a suite of associated bone and dental pathologies. Further damage to the jaw joint may have been the cause of death.     

Iatrogenic transmission of Cytauxzoon felis from a Florida panther (Felix concolor coryi) to a domestic cat

A laboratory cat died 12 days after intraperitoneal inoculation of a 1 ml suspension containing 1.5 x 10(6) blood mononuclear cells from a Florida panther (Felis concolor coryi). Gross, histologic and ultrastructural investigations revealed the cause of death to be infection by Cytauxzoon felis, a protozoal parasite known to cause a rapidly fatal disease (cytauxzoonosis) in domestic cats. The bobcat (Felis rufus) has been identified as a natural host for C. felis. This report implicates the Florida panther as another possible host for C. felis.     

Material changes in osteoporotic human cancellous bone following infiltration with acrylic bone cement for a vertebral cement augmentation

Bone cement infiltration can be effective at mechanically augmenting osteoporotic vertebrae. While most published literature describes the gain in mechanical strength of augmented vertebrae, we report the first measurements of viscoelastic material changes of cancellous bone due to cement infiltration. We infiltrated cancellous core specimen harvested from osteoporotic cadaveric spines with acrylic bone cement. Bone specimen before and after cement infiltration were subjected to identical quasi-static and relaxation loading in confined and free compression. Testing data were fitted to a linear viscoelastic model of compressible material and the model parameters for cement, native cancellous bone, and cancellous bone infiltrated (composite) with cement were identified. The fitting demonstrated that the linear viscoelastic model presented in this paper accurately describes the mechanical behaviour of cement and bone, before and after infiltration. Although the composite specimen did not completely adopt the properties of bulk bone cement, the stiffening of cancellous bone due to cement infiltration is considerable. The composite was, for example, 8.5 times stiffer than native bone. The local stiffening of cancellous bone in patients may alter the load transfer of the augmented motion segment and may be the cause of subsequent fractures in the vertebrae adjacent to the ones infiltrated with cement. The material model and parameters in this paper, together with an adequate finite-element model, can be helpful to investigate the load shift, the mechanism for subsequent fractures, and filling patterns for ideal cement infiltration.     

Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid

Excess exogenous retinoic acid (RA) has been well documented to have teratogenic effects in the limb and craniofacial skeleton. Malformations that have been observed in this context include craniosynostosis, a common developmental defect of the skull that occurs in 1 in 2500 individuals and results from premature fusion of the cranial sutures. Despite these observations, a physiological role for RA during suture formation has not been demonstrated. Here, we present evidence that genetically based alterations in RA signaling interfere with human development. We have identified human null and hypomorphic mutations in the gene encoding the RA-degrading enzyme CYP26B1 that lead to skeletal and craniofacial anomalies, including fusions of long bones, calvarial bone hypoplasia, and craniosynostosis. Analyses of murine embryos exposed to a chemical inhibitor of Cyp26 enzymes and zebrafish lines with mutations in cyp26b1 suggest that the endochondral bone fusions are due to unrestricted chondrogenesis at the presumptive sites of joint formation within cartilaginous templates, whereas craniosynostosis is induced by a defect in osteoblastic differentiation. Ultrastructural analysis, in situ expression studies, and in vitro quantitative RT-PCR experiments of cellular markers of osseous differentiation indicate that the most likely cause for these phenomena is aberrant osteoblast-osteocyte transitioning. This work reveals a physiological role for RA in partitioning skeletal elements and in the maintenance of cranial suture patency.     

Material Changes in Osteoporotic Human Cancellous Bone Following Infiltration with Acrylic Bone Cement for a Vertebral Cement Augmentation

Bone cement infiltration can be effective at mechanically augmenting osteoporotic vertebrae. While most published literature describes the gain in mechanical strength of augmented vertebrae, we report the first measurements of viscoelastic material changes of cancellous bone due to cement infiltration. We infiltrated cancellous core specimen harvested from osteoporotic cadaveric spines with acrylic bone cement. Bone specimen before and after cement infiltration were subjected to identical quasi-static and relaxation loading in confined and free compression. Testing data were fitted to a linear viscoelastic model of compressible material and the model parameters for cement, native cancellous bone, and cancellous bone infiltrated (composite) with cement were identified. The fitting demonstrated that the linear viscoelastic model presented in this paper accurately describes the mechanical behaviour of cement and bone, before and after infiltration. Although the composite specimen did not completely adopt the properties of bulk bone cement, the stiffening of cancellous bone due to cement infiltration is considerable. The composite was, for example, 8.5 times stiffer than native bone. The local stiffening of cancellous bone in patients may alter the load transfer of the augmented motion segment and may be the cause of subsequent fractures in the vertebrae adjacent to the ones infiltrated with cement. The material model and parameters in this paper, together with an adequate finite-element model, can be helpful to investigate the load shift, the mechanism for subsequent fractures, and filling patterns for ideal cement infiltration.     

Joint model for recurrent event data with a cured fraction and a terminal event

In a longitudinal study where the recurrence of an event and a terminal event such as death are observed, a certain portion of the subjects may experience no event during a long follow-up period; this often denoted as the cure group which is assumed to be the risk-free from both recurrent events and death. However, this assumption ignores the possibility of death, which subjects in the cure group may experience. In the present study, such misspecification is investigated with the addition of a death hazard model to the cure group. We propose a joint model using a frailty effect, which reflects the association between a recurrent event and death. For the estimation, an expectation-maximization (EM) algorithm was developed and PROC NLMIXED in SAS was incorporated under a piecewise constant baseline. Simulation studies were performed to check the performance of the suggested method. The proposed method was applied to leukemia patients experiencing both infection and death after bone marrow transplant.     

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

Introduction  

Subchondral bone cysts (SBC) have been identified in patients with knee osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA.     

Lagomorph abundance around yellow-eyed penguin (

Predation of yellow-eyed penguin (Megadyptes antipodes) chicks may be reduced by removing stock around penguin breeding sites because long grass may reduce lagomorph abundance and hence small mammal predators. This study tests this hypothesis in the South Island, New Zealand. The abundance of lagomorph faeces (mainly rabbit Oryctolagus cuniculus, but some European hare Lepus europaeus) was used as an index of relative abundance of lagomorphs at 16 penguin breeding sites in winter 1991 and 37 sites in 1992/93. There was no evidence that lagomorph pellet abundance was reduced where vegetation was ungrazed. Lagomorph sign was widespread throughout ungrazed areas indicating that the entire ungrazed area and not merely the edge was used by lagomorphs. Lagomorph pellet abundance was higher on sand dunes than elsewhere. Retirement from grazing by stock may help protect and provide nesting habitat for penguins, but does not decrease lagomorph abundance close to nesting sites. Iris not yet known whether high lagomorph abundance leads to increased or decreased predation on penguin chicks. The habitat should not be modified ostensibly to reduce lagomorph abundance until the effect on predation is known.     

A probable case of prehistoric kidney stone disease from the northern Cape Province, South Africa

During the excavation of isolated graves along the north shore of the Orange River in the Cape Province of South Africa, a skeleton was uncovered that showed two large calcareous deposits near the lumbar region of the vertebral column. The individual was an adult female of about 55 years of age at the time of death. The calcified residue did not in any way resemble the external or internal anatomical form of a kidney, but X-ray powder diffraction analysis and scanning electron microscopy identified the material as apatite (Ca10(PO4)6 (OH)2), a common constituent of human urinary calculi. It is postulated that the bilateral calcification was the result of a chronic renal disorder. Although it is rarely possible to identify the cause of death from skeletal remains alone, the disorder as seen in this specimen would appear to have been very severe and may well have been the ultimate cause of death.     

MAPKKKalpha is a positive regulator of cell death associated with both plant immunity and disease

Many plant pathogens cause disease symptoms that manifest over days as regions of localized cell death. Localized cell death (the hypersensitive response; HR) also occurs in disease-resistant plants, but this response appears within hours of attempted infection and may restrict further pathogen growth. We identified a MAP kinase kinase kinase gene (MAPKKKalpha) that is required for the HR and resistance against Pseudomonas syringae. Significantly, we found that MAPKKKalpha also regulates cell death in susceptible leaves undergoing P. syringae infection. Overexpression of MAPKKKalpha in leaves activated MAPKs and caused pathogen-independent cell death. By overexpressing MAPKKKalpha in leaves and suppressing expression of various MAPKK and MAPK genes by virus-induced gene silencing, we identified two distinct MAPK cascades that act downstream of MAPKKKalpha. These results demonstrate that signal transduction pathways associated with both plant immunity and disease susceptibility share a common molecular switch.     

The late Miocene mammals from the Konservat-Lagerstätte of Saint-Bauzile (Ardèche,France)

Diatomite deposits of Saint-Bauzile near Privas (Ardèche) in southern France have been known since more than two centuries for abundant and extremely well-preserved fossils of plants and animals. The radiometric dating brackets fossil-bearing horizons between 7.2 and 7.6 Ma, which is consistent with the biochronologic age given by fossil mammals, which are characteristics of the late MN11 zone, i.e. the second part of the late Miocene. The main interest of this site for mammals is that they are preserved almost “in the flesh”, as entire skeletons with bones in their anatomical connection, and often with skin and fur charred and forming a halo around the body. In this work, we studied the remains of a lagomorph, two rodents, an equid, a suid, a bovid and a rhino. The mode of preservation of mammals as entire bodies suggests sudden death and rapid burial of individuals.     

Differential diagnosis of Charcot arthropathy and osteomyelitis

Foot problems are common causes of morbidity in patients with diabetes mellitus. Foot ulcers are the leading cause of hospitalization in diabetic patients. Bones may be involved in two different clinical conditions: osteomyelitis and Charcot osteoarthropathy. Osteomyelitis usually develops by spreading from contiguous soft tissue to underlying bone. Charcot foot is deformation of foot as a result of muscle athrophy, bone and joint structure changes in a joint as a secondary complication of neuropathy. To distinguish bone infection from non-infectious bone disorders as in Charcot joint may be difficult, especially if there is no skin ulceration. So, the mere absence of skin ulcers does not exclude the diagnosis of osteomyelitis.     

Paracoccidioidomycosis Induced by Immunosuppressive Drugs in a Patient with Rheumatoid Arthritis and Bone Sarcoma: Case Report and Review of the Literature

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, which is endemic in many regions of Latin America. We describe the case of a 60-year-old man from a region endemic for PCM who presented with a long history of left hip pain. He had been treated over the past 3 years with immunosuppressive drugs (methotrexate, leflunomide, and adalimumab) for rheumatoid arthritis (RA). A hip radiograph showed lytic bone lesions, and a chest radiograph showed an expansive excavated lesion in the left lung, suggestive of a lung cancer with bone metastases. A left hip joint biopsy was inconclusive, but histological analysis of a surgical lung biopsy specimen was consistent with P. brasiliensis infection. Treatment with intravenous amphotericin B (50 mg/day) and hydrocortisone (25 mg/day) was initiated. However, increasing hip pain resulted in the amputation of the left lower limb, and the analysis of the surgical specimen revealed a diagnosis of bone sarcoma. Postoperatively, the patient developed sepsis and died approximately 1 month later. To our knowledge, this is the first report of PCM in a patient with RA who had been treated with immunosuppressive drugs, in particular TNF-α blocking agents. The atypical presentation (left hip pain alone) emphasizes the importance of considering PCM in the differential diagnosis of patients with pulmonary lesions and osteolytic lesions who live in a region endemic for PCM. This case report also demonstrates that health professionals in these regions must pay close attention to patients receiving immunosuppressive drugs because of the possibility of reactivating quiescent P. brasiliensis lesions.     

The effectiveness of bone banking in Central Serbia: audit of the first seven years

We analyzed the incidence and predisposing factors for overall discard rate after retrieval of 295 femoral head allografts. The aim of the present study was to evaluate the quality system of institutional bone banking and to ensure that we can provide high standard allografts with low infection rate. Audit of bone banking was conducted on 295 donors and 180 recipients. Of the 295 donated femoral heads 77 were discarded, giving an overall discard rate of 26.1 %. At retrieval, 37 allografts were positive, giving an overall contamination rate of 12.54 %. The organism most commonly identified was Staphylococcus species. Seven (2.37 %) of the 295 allografts failed the blood screening tests. Twelve allografts (4.06 %) were discarded because of suspected damage of the packaging or disuse during surgery. Due to donor death or inability to perform serology retests, 21 (7.11 %) allografts were discarded. In the postoperative survey an infection rate of 2.22 % was found. After 7 years of bone banking, our results show that overall discard rate and allograft related infection rate are in accordance with the international standards. The leading cause of allograft discarding was bacterial contamination influenced by the surgical team. We suggest stringent aseptic allograft handling during harvesting and thawing within highly concentrated antibiotic solution to reduce a possibility of its contamination.     

Laboratory confirmation of a suspicious meningococcal meningitis death case

A suspicious meningococcal meningitis death case was reported to the Beijing CDC. The blood specimen was analyzed via multi-PCR and MLST. 6 isolates from close contacts were analyzed via PFGE and MLST. According to the results of the above analyses, the cause of this case was identified as a serogroup A Neisseria meningitidis, which, in terms of sequence typing, belonged the ST7 group.