Thrombophilias and adverse pregnancy outcomes: results from the Danish National Birth Cohort.

BACKGROUND: Inherited thrombophilias have inconsistently been linked to adverse pregnancy outcomes. Differences in study design, size and population could explain this heterogeneity. OBJECTIVE: The aim of the present study was to evaluate if factor (F)V Leiden G1691A, prothrombin mutation G20210A (PTM) and methylenetetrahydrofolate reductase C677T (MTHFR) increased the risk of severe preeclampsia, fetal growth restriction, very preterm delivery, placental abruption and a composite of these outcomes also including stillbirth. PATIENTS AND METHODS: In a nested case-cohort study of pregnant women in Denmark, we genotyped 2032 cases and 1851 random controls. Each of the medical records of the cases was validated. We calculated both genomic and allelic models, and present both models. We also performed sensitivity analyses adjusting for parity, age, smoking, body mass index and socioeconomic status. RESULTS: In the allelic models, FV Leiden increased the risk of the composite outcome (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1-1.8), severe preeclampsia (OR 1.6, 95% CI 1.1-2.4), fetal growth restriction (OR 1.4, 95% CI 1.1-1.8) and placental abruption (OR = 1.7 (95% CI 1.2-2.4). In the sensitivity analyses, adjustment diminished these estimates slightly. PTM was not significantly associated with any of the outcomes, and MTHFR was only significantly associated with severe preeclampsia (OR 1.3, 95% CI 1.1-1.6). CONCLUSION: FV Leiden predisposes to adverse pregnancy outcomes in a setting of Scandinavian women.

Bone eburnation in rheumatic diseases: a guiding trace in today's radiological diagnosis and in paleopathology.

Bone eburnation is a common anatomical trace of chronic arthropathy. However, its topographical analysis in rheumatic diseases can contribute to knowledge about the latter, by explaining today's diagnosis through radiology as well as by giving an historical perspective through paleopathology. After recalling that eburnated areas can also originate in infectious arthritis, the present analysis consists in a comparison between macroscopic and radiological observations of both osteoarthritis (OA) and rheumatoid arthritis (RA) at an advanced stage. It focuses on the human femoral head because of its demonstrative interest. Two main observations emerge from our study. The eburnated surface is less extensive in OA (where it appears to be essentially linked to the original structure of the hip) and more extensive in RA at an advanced stage (where an additional systemic factor is predominant). The size of the associated osteophytes appears to be inversely proportional to the extent of the corresponding eburnated area. In connection with the OA-RA comparison above, the contribution of the original joint structure to bone eburnation was also illustrated by acromiohumeral eburnation in shoulder OA and by the comparison with dog hip OA. It must also be noted that a femoral head bone remodeling similar on the whole to that of OA can occur in ochronotic arthropathies whose causal chondropathy is due to a genetic defect. Originating in an identified chondropathy, eburnation in ochronotic arthropathy gives us the opportunity to study an OA-type bone remodeling per se as in an experiment supplied by nature and involving a human hip. However, since RA and ochronotic arthropathy are due to a diffuse chondropathy, both may create a similar macroscopic (and thus radiological) eburnation topography.

Magnesium whitlockite, a calcium phosphate crystal of special interest in pathology.

Whitlockite (in fact magnesium whitlockite) is a calcium orthophosphate crystal in which, in biological conditions, magnesium is partly substituted for calcium. Identified in X-ray or electron diffraction patterns, it occurs in physiological or pathological conditions at extra or intratissular sites, mainly in tissues of non-epithelial origin. In a range of pathological calcifications investigated by X-ray diffraction, we noted that whitlockite appeared to be frequently associated with apatite, particularly in "dystrophic calcifications" of tuberculous origin. These personal observations could be correlated with documented data in oral pathology (dental calculus, salivary stones, and dental caries). Whitlockite deposits have also been reported in non-infectious conditions, such as in aortic media, cartilage, and bone tissue. Whereas the formation of both apatite and magnesium whitlockite appears to be caused by the binding of their constituting ions with proteolipids, magnesium inhibits apatite originating from amorphous calcium phosphate to the benefit of whitlockite formation. Possibly, the development of magnesium whitlockite may provide an interesting marker for magnesium metabolism. Further studies linking histology to crystallography might relate the crystal to issues, such as tuberculous calcifications or diseases of bone tissue, and might be useful for potential diagnostic orientation.

Nosology versus pathology, two approaches to rheumatic diseases illustrated by Alfred Baring Garrod and Jean-Martin Charcot.

OBJECTIVES: To show why and how, without underestimating the popular perception of the word 'rheumatism', a medical approach to rheumatic diseases needs to consider the distinction between nosology (the study of diseases) and pathology [anatomopathology (the study of lesions) and physiopathology (the study of functional disturbances)]. METHODS: Selected quotations reflecting the thought processes of two famous physicians whose clinical activity (orientated towards nosology) was firmly based on pathology (mainly physiopathology in the case of A. B. Garrod and mainly anatomopathology in the case of J.-M. Charcot) are discussed. RESULTS: Starting from the physiopathological criterion of hyperuricaemia in gout, Garrod's thought processes led him to name and study rheumatoid arthritis. Alongside his neurological work, Charcot's thought processes led him to underline the common anatomical changes which could be observed in some nosologically distinct forms of chronic rheumatism. CONCLUSIONS: Selected older texts of both authors provide good examples of a methodology which can still be useful for present-day rheumatologists, particularly during their training period. They could serve as a guide to clarify some semantic ambiguities concerning nosology and pathology and for a better understanding of some clinical and radiological overlaps between distinct nosological entities.

Metastatic carcinoma of presumed prostatic origin in cremated bones from the first century A.D.

A cremated pelvis dating from the first century A.D. showed evidence of osteosclerotic metastasis, presumably secondary to prostate carcinoma. The case demonstrates the importance of microradiography in palaeopathology as well as some of the structural changes seen in cremated bone.

Synovial cyst and degeneration of the transverse ligament: an unusual cause of high cervical myelopathy. Case report.

A case of cystic degeneration of the transverse ligament located posteriorly to the dens and causing compression to the lower medulla and upper cervical spinal cord is reported. The clinical, pathological, and radiological findings are described and compared to the literature to characterize this syndrome more fully. The advantages of a posterolateral surgical approach are stressed.

The enduring mark left by Jean-Martin Charcot on rheumatology.

Although Charcot is remembered above all as an outstanding neurologist, he also left a lasting imprint on the study of rheumatic diseases, primarily in two fields. a) He performed a pathologic-nosographic confrontation based on principles that remain relevant in today's era of imaging techniques. His vision as a pathologist allowed him to establish links between nonspecific lesions, which led him to develop a unified concept of chronic rheumatism. At the same time however, his experience as a clinician gave him a sense of the nosologic distinctions that are widely accepted today. b) He analyzed osteoarticular dystrophies associated with neurologic disorders, most notably tabetic arthropathies with epiphyseal fragmentation and in some instances spontaneous fractures. In addition, a constellation of alterations of the synovial membrane, ligaments, and muscles identified in those analyses foreshadowed today's concept of reflex sympathetic dystrophy syndrome.

Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs.

Chronic liver disease due to hepatitis C virus (HCV) infection is a major problem in hemophiliacs. Recent reports suggested that hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus (HIV) have an increased incidence of liver failure but the mechanism of accelerated liver injury is not clear. We tested plasma from 100 hemophiliacs for anti-HCV by second generation ELISA, anti-HIV by EIA, and HCV RNA and HIV RNA by branched DNA and polymerase chain reaction assays to determine if hemophiliacs coinfected with HCV and HIV have higher HCV RNA levels and more active liver disease. Seventy-nine (79%) patients were anti-HCV positive, of whom 85% were HCV RNA positive. None of the anti-HCV-negative patients had detectable HCV RNA in plasma. Forty-two (42%) patients were anti-HIV positive, of whom 47% had detectable HIV RNA. All the anti-HIV-positive patients were also anti-HCV positive. The prevalence of both anti-HCV and anti-HIV increased significantly with age. There was no difference in HCV RNA levels between anti-HIV-positive and anti-HIV-negative patients (mean: 21 +/- 4 vs 18 +/- 5 Meq/ml), although HCV RNA levels were significantly higher in anti-HIV-positive patients with CD4 counts < 200/mm3 (P = 0.008). There was an inverse correlation between HCV RNA levels and CD4 counts but no correlation was found between HCV RNA and serum aminotransferase levels. We found a high prevalence of HCV and HIV coinfection in our hemophiliacs. Hepatitis C virus replication appears to be increased in patients with severe immunodeficiency secondary to progressive HIV infection. However, there was no correlation between HCV RNA and serum ALT level, suggesting that HCV is not directly cytopathic.

Accurate quantification of hepatitis C virus (HCV) RNA from all HCV genotypes by using branched-DNA technology.

In studies monitoring disease progression and therapeutic response, it is essential that the method used for hepatitis C virus (HCV) quantification not be influenced by genotypic variability. The branched DNA assay provides a reliable method for the quantification of HCV RNA. A modified set of oligonucleotide probes for the branched DNA assay was developed to enhance the efficiency of binding to genotypic variants of HCV. The improved branched DNA assay (HCV RNA 2.0) yielded highly reproducible quantification of hepatitis C virus RNA and displayed a nearly 600-fold dynamic range in quantification up to 120 Meq of HCV RNA per ml. The quantification limit was set at 0.2 Meg of HCV RNA per ml to ensure a specificity of > or = 95%. With this lowered quantification limit and the enhanced hybridization of the probes, the HCV RNA 2.0 assay exhibited a high level of sensitivity (96%) and was virtually unaffected by the genotypic variability of HCV. The HCV RNA 2.0 assay may be a useful tool for following HCV RNA levels throughout the course of disease, selecting patients for therapy, and evaluating therapeutic response.

Pathological anatomy in the teaching of rheumatology.

Whereas rheumatology regroups nosological entities, its teaching must be partly based on a presentation of the corresponding anatomopathological aspects which in fact are various patchworks made up of elementary, generally nonspecific lesions of osteoarticular pathology. Such an approach will provide an objective guideline between the needs of the practitioner (who often thinks in terms of morphology through radiological images) and the plethora of modern basic data. Thus the methods can be adapted to the needs of various audiences (medical students, specialists in training, paramedical personnel) and to every material and financial possibilities. In all cases it must be integrated with clinical and radiological lectures, based on macroscopic and radiological correlations and complemented, as far as possible, with appropriate histological images.

Rheumatism as perceived by some quotations: as seen by the patient and physician.

The word "rheumatism", introduced in ancient times, is still used directly or indirectly, in parallel with the terms of the modern nosography. The reasons for this persistence can be sought in the history of the concept, which can be approached via quotations from texts written either by authors who describe popular beliefs or their own sufferings; or by physicians known to have played a prominent role in the individualization of rheumatology. The word "rheumatism" was first used mainly to designate a painful fluxion of the tissues located between the skin and the internal organs. It gradually lost ground to more descriptive terms suggestive of joints. Thus, the concept of "rheumatism" still bears the hallmark of its "popular" roots and is on a level parallel to but distinct from that of modern nosography. Awareness of its origins may improve communication between physicians and patients and also raises questions about the foundations of the concept of "rheumatic disease".

Evaluation of branched DNA signal amplification for the detection of hepatitis C virus RNA.

There is an increasing need for a practical assay to measure HCV RNA to assess the viral burden in chronic hepatitis C virus (HCV) infection as viral load relates to transmission and therapeutic response. This study evaluates branched DNA (bDNA) signal amplification, a technique that avoids many of the pitfalls of polymerase chain reaction (PCR). The bDNA assay uses a microtitre well format and a series of capture, target and amplification probes that bind RNA to the well and then successively bind oligonucleotides to the RNA and branched DNA molecules to the oligonucleotides. Enzyme-labelled probes are bound to the arms of the bDNA and light output from a chemiluminescent substrate is directly proportional to the amount of starting HCV RNA. Appropriate standards provide direct quantitation. Whereas PCR amplifies the HCV genome, bDNA amplifies the hybridization signal. In testing a standardized, coded panel, bDNA showed 100% specificity and detected five of six sera proven to transmit hepatitis C to the chimpanzee; PCR detected all six infectious sera. Serial samples were measured in two acute and five chronic cases of transfusion-associated hepatitis and in three commercial seroconversion panels. In acute cases, 10(7)-10(8) molecular equivalents per ml (eq per ml) of HCV RNA were detected prior to peak alanine aminotransferase (ALT) activity and then rapidly declined to non-detectable levels. Similar levels of HCV RNA were observed early in the course of two patients who progressed to chronic hepatitis; the chronic course was characterized by diminished, fluctuating and sometimes non-detectable levels of HCV RNA. In two chronic cases, HCV RNA was not detected, or only transiently detected by bDNA, but was present when assayed by PCR. In one chronic case, the periodicity of HCV RNA levels closely paralleled the fluctuations of ALT suggesting a relationship between viral replication and subsequent hepatocellular injury. In testing 50 blood donors whose anti-HCV reactivity was confirmed by a recombinant immunoblot assay (RIBA), HCV RNA was detected by bDNA in 41 (81%), while PCR was positive in 45 (90%); the overall concordance between bDNA and PCR in 100 anti-HCV enzyme immunoassays (EIA) reactive donor samples was 96%.(ABSTRACT TRUNCATED AT 400 WORDS)

Case report 719. Reaction of synovium and bone to a silicone implant of the lunate.

A radiological and histological study of synovitis and bone invasion due to deterioration of a silicone implant of the lunate is presented. The interest of similar observations for osteoarticular pathology is discussed.

Rheumatic diseases in Neolithic and Medieval populations of western Switzerland.

An investigation of three groups from ancient populations (Neolithic, Early Middle Ages, Middle Ages) was performed on 273 adult skeletons. Despite unequal preservation of the remains, a study of a series of large joints and spinal segments permitted some conclusions: rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis of large joints (hip, knee, shoulder) were not found. The main findings were: osteoarthrosis in spinal zygapophyseal joints (particularly at cervical level); intervertebral osteochondrosis (particularly at the cervical and lumbar levels); Schmorl's nodes (particularly at the thoracic and lumbar levels); enthesopathic osteophytes (particularly in the spine, iliac crest, patella, and calcaneus). Such deformities seemed more frequent in the Middle Ages than in the Neolithic period.