For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. ____and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional “number of criteria present” format and “classification tree” techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation ≥15º, pain present on internal rotation of the hip, morning stiffness of the hip for ≤60 minutes, and age >50 years, or 2) hip internal rotation <15º and an erythrocyte sedimentation rate (ESR) ≤45 mm/hour; if no ESR was obtained, hip flexion ≤115º was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR <20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The “number of criteria present” format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an ostophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.

Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multi- center study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the "classification tree" method were 92% sensitive and 98% specific. The "traditional format" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands.To promote uniformity in the reporting of the rheumatic diseases, the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology established subcommittees to develop classification criteria. During the last decade, criteria for systemic sclerosis, Reiter's syndrome, systemic lupus er ythematosus, rheumatoid arthritis (RA), osteoart hri-

Objective. A dose-response relationship for hydroxychloroquine (HCQ), in terms of the proportion of patients achieving the Paulus 20% criteria for improvement, had previously been observed in patients with rheumatoid arthritis (RA) receiving a 6-week loading regimen of 400, 800, or 1,200 mg HCQ daily. This present retrospective analysis was performed to investigate possible relationships between the blood HCQ and HCQ-metabolite concentrations and measures of efficacy and toxicity. In addition, we sought to ascertain whether further investigation of HCQ/HCQ-metabolite levels might lead to testing of one of these substances as a new antirheumatic drug.Methods. Patients with active RA (n ‫؍‬ 212) began a 6-week, double-blind trial comparing 3 different doses of HCQ at 400, 800, or 1,200 mg/day, followed by 18 weeks of open-label HCQ treatment at 400 mg/day. Patients were repeatedly evaluated for treatment efficacy and toxicity. Blood samples were available from 123 patients for analysis of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ) levels using highperformance liquid chromatography. Achievement of the modified Paulus 20% improvement criteria for response in RA was used as the primary efficacy parameter. Spontaneously reported adverse events were categorized and analyzed as toxicity outcome variables. The relationship between response (efficacy and toxicity) and drug levels was evaluated using logistic regression analysis.Results. The subset of patients with blood concentration data was equivalent to the larger study population in all demographic and outcome characteristics. The mean HCQ, DHCQ, and DCQ elimination halflives were 123, 161, and 180 hours, respectively. There was a positive correlation between the Paulus 20% improvement criteria response and blood DHCQ concentrations during weeks 1-6 (P < 0.001). A potential relationship between ocular adverse events and BDCQ levels was found (P ‫؍‬ 0.036). Logistic regression analysis of adverse events data showed that adverse gastrointestinal events were associated with higher HCQ levels (P ‫؍‬ 0.001-0.021) during weeks 1, 2, and 3.

Hyperostosis frontalis interna (HFI) is manifested by the accretion of bone on the inner table of the frontal bone. Despite the vast literature on HFI, ambiguity exists as to its etiology, osteogenesis, demography, and history. This stimulated the present broad-scale study of HFI which included the evaluation of 1,706 early 20th century skulls (1,007 males and 699 females) from the Hamann-Todd and Terry human osteological collections, as well as 2,019 pre-19th century East-Mediterranean, Amerindian, and Central European skulls. In addition, 72 cadavers were dissected for gross inspection and histology. Special attention was paid to the relationship of the brain and meninges to endocranial lesions. HFI is an independent condition, not a symptom of a more generalized syndrome as suggested in the past. It can appear in a variety of forms but each is the result of the same process and probably of the same etiology. Investigators' previous failure to recognize the mild stages of HFI (types A and B) as an early form of the general HFI process led to erroneous statistics and interpretations of observations. HFI should also be considered a phenomenon separate from HCI, hyperostosis cranialis diffusa (HCD), and other endostoses, even when it appears in association with them. To avoid ambiguity and facilitate the description of cranial hyperostoses, uniform nomenclature (HFI, HCD) has been recommended. HFI is rarely seen in historic populations, regardless of geographical origin. It is most commonly found among females and is believed to be associated with prolonged estrogen stimulation. While its magnitude of manifestation and frequency are much higher in females, HFI is not a purely female phenomenon. Males with hormonal disturbances such as atrophic testis were found to manifest HFI type D. HFI is associated with age insofar as it is much less frequent in females under 40 years of age. Although advanced cases of HFI (types C and D) have been observed in individuals as young as 40 years of age, it is more frequently found after age 60. The frequency of HFI type D will not increase from age 60. Type-predicted analysis by cohort reveals significant ethnic differences. Changes in African American (AA) females appear earlier in life and progress more rapidly than in European American (EA) females. Analysis of radiographs shows a discrepancy between the anatomic prevalence of HFI and its radiological recognition, which is very poor for mild cases. This apparently resulted in the misconceptions that HFI is entirely an old-age phenomenon, and that it is exclusively female. Histological analysis shows that the inner table along with the closely attached dural layer play a major role in the osteogenesis of HFI. Contrary to previous models, no evidence for diploe or ectocranial plate involvement was found. Cadaver study suggests that the predilection for the frontal area may be related to an altered blood supply and/or vascular stretching.

In order to assess the presence of tuberculosis in Pleistocene bison and the origin of tuberculosis in North America, 2 separate DNA extractions were performed by 2 separate laboratories on samples from the metacarpal of an extinct long-horned bison that was radiocarbon dated at 17,870+/-230 years before present and that had pathological changes suggestive of tuberculosis. Polymerase chain reaction amplification isolated fragments of tuberculosis DNA, which were sequenced, and on which spoligotyping was also performed to help determine its relationship to the various members of the Mycobacterium tuberculosis complex. Extensive precautions against contamination with modern M. tuberculosis complex DNA were employed, including analysis of paleontologic and modern specimens in 2 geographically separate laboratories.

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Tracing the evolution of ancient diseases depends on the availability and accessibility of suitable biomarkers in archaeological specimens. DNA is potentially information-rich but it depends on a favourable environment for preservation. In the case of the major mycobacterial pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, robust lipid biomarkers are established as alternatives or complements to DNA analyses. A DNA report, a decade ago, suggested that a 17,000-year-old skeleton of extinct Bison antiquus, from Natural Trap Cave, Wyoming, was the oldest known case of tuberculosis. In the current study, key mycobacterial lipid virulence factor biomarkers were detected in the same two samples from this bison. Fluorescence high-performance liquid chromatography (HPLC) indicated the presence of mycolic acids of the mycobacterial type, but they were degraded and could not be precisely correlated with tuberculosis. However, pristine profiles of C29, C30 and C32 mycocerosates and C27 mycolipenates, typical of the Mycobacterium tuberculosis complex, were recorded by negative ion chemical ionization gas chromatography mass spectrometry of pentafluorobenzyl ester derivatives. These findings were supported by the detection of C34 and C36 phthiocerols, which are usually esterified to the mycocerosates. The existence of Pleistocene tuberculosis in the Americas is confirmed and there are many even older animal bones with well-characterised tuberculous lesions similar to those on the analysed sample. In the absence of any evidence of tuberculosis in human skeletons older than 9,000 years BP, the hypothesis that this disease evolved as a zoonosis, before transfer to humans, is given detailed consideration and discussion.