Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis.

OBJECTIVE: A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. METHODS: Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). RESULTS: RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. CONCLUSIONS: We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells.

Musculoskeletal education in general practice: a questionnaire survey.

Musculoskeletal education in primary care has previously been shown, in 1995, to be inadequate [1]. The aims of this study were to evaluate the current musculoskeletal education and skills during vocational training for general practice and to see if progress has been made. Questionnaires were sent to General Practice Registrars, in general practice attachments in June 2004. Four UK General Practice Deaneries participated (Northern, Mersey, Yorkshire and Wessex). Questionnaires were received from 251 (44 %) registrars. Of the responders, only 77 % reported receiving specific clinical rheumatology teaching at medical school and 30 % had not received any tutorials on musculoskeletal conditions during their vocational training. Of the registrars, 16 % reported having completed a rheumatology post, and an additional 19 % had been able to attend rheumatology outpatient clinics; 70 % of the registrars had injected or aspirated the knee although less than half of these (22 %) had done this in a primary care setting. Lack of experience was associated with low confidence at knowing when to perform the injection and with performing the injection itself. A significant proportion of registrars reported being pre-dominantly self-taught for performing injections (soft tissue = 10.7 %, joint injections = 8.7 %) and for the management of shoulder pain (20.1 %). Registrars rated their overall musculoskeletal training as inadequate. Primary care musculoskeletal education remains inadequate and needs to be improved to enable registrars to be confident in managing a significant proportion of their workload. Identifying learning needs for primary care would inform future educational interventions.

Musculoskeletal screening examination (pGALS) for school-age children based on the adult GALS screen.

OBJECTIVE: To develop and validate a musculoskeletal screening examination applicable to school-age children based on the adult Gait, Arms, Legs, Spine (GALS) screen. METHODS: Adult GALS was tested in consecutive school-age children attending pediatric rheumatology clinics and was compared with an examination conducted, on the same day, by a pediatric rheumatologist who classified children as having abnormal or normal joints. Adult GALS was tested for validity compared with the pediatric rheumatologist's assessment and deficiencies in adult GALS were identified. Experts proposed amendments to adult GALS, achieving consensus by modified Delphi techniques. The resultant pediatric screening tool (pGALS) was tested (methodology identical to the testing of adult GALS) in an additional group of children. RESULTS: Adult GALS was tested in 50 children (median age 11 years, range 4-16), of whom 37 (74%) had juvenile idiopathic arthritis. Adult GALS missed important abnormalities in 18% of children, mostly at the ankle, foot, and temporomandibular joints. The pGALS was tested in 65 children (median age 13 years, range 5-17 years) and demonstrated excellent sensitivity (97-100%) and specificity (98-100%) at all joints, with high acceptability scored by child and parent/guardian. The median time to perform pGALS was 2 minutes (range 1.5-3 minutes). CONCLUSION: The pGALS musculoskeletal screening tool has excellent validity, is quick to perform, and is acceptable to school-age children and parents/guardians. We propose that pGALS be incorporated into undergraduate and postgraduate medical training to improve pediatric musculoskeletal clinical skills and facilitate diagnosis and referral to specialists.

Teaching medical students musculoskeletal examination skills: identifying barriers to learning and ways of overcoming them.

OBJECTIVES: To elicit the barriers to the effective teaching of musculoskeletal examination skills amongst medical students. METHODS: This was a qualitative study including six focus groups with specialities most often involved in delivering musculoskeletal clinical teaching: rheumatology, orthopaedics, general practice, and geriatrics. RESULTS: The main barriers to the delivery of effective clinical teaching included the lack of agreement on what to teach, lack of confidence in teaching amongst non-musculoskeletal specialities, and poor communication between specialities. CONCLUSIONS: There is a need to overcome the identified barriers if musculoskeletal clinical teaching to medical students is to be improved. In particular, there is a need to agree which examination skills medical students should learn.

Regional Examination of the Musculoskeletal System (REMS): a core set of clinical skills for medical students.

OBJECTIVES: The aim of this study was to determine an agreed set of core regional musculoskeletal examination skills for medical students to learn. METHODS: Initially focus groups were undertaken amongst Rheumatologists, Orthopaedic Surgeons, Geriatricians and General Practitioners. These findings were used to inform the production of a questionnaire survey. The findings from both the questionnaire survey and focus groups were assessed using a group nominative technique with national representation from each of the four specialties involved. RESULTS: This process has led to the identification of 50 items, considered to be core regional musculoskeletal examination skills for medical students. CONCLUSIONS: This core set of musculoskeletal clinical skills may now be used to inform the production of teaching materials aimed at medical students.

Joints: if relevant. Do available textbooks contain adequate information about musculoskeletal examination skills for medical students?

The objective was to determine whether routinely available textbooks describe the core musculoskeletal examination skills for medical students. Textbooks were evaluated for content against a list of 27 core examination skills as perceived by rheumatologists, orthopaedic surgeons and general practitioners. The study took place in Newcastle upon Tyne, libraries of the rheumatology department, teaching hospital and medical school. The main outcome was the inclusion of a description of examination skills by available textbooks. Median score for each textbook was only 19 (range 1-24) of a possible 27 core skills. Screening examination was not included in general texts. General principles were well covered but detail was insufficient, particularly in texts aimed at students taking final examinations. It is not easy for students to access adequate information about core items of musculoskeletal examination from textbooks readily available to them. This may reflect a general view of the lack of importance of musculoskeletal clinical examination skills.

Portable breath alcohol testers and drinking-driving behavior of convicted drunk drivers.

The use of portable breath alcohol testers by convicted drunk drivers during a drinking-driving educational program had a nonsignificant impact on the frequency of drinking-driving episodes. The use of breath alcohol testers also failed to significantly reduce peak blood alcohol concentration during drinking-driving episodes. However, portable breath testers were used by certain drunk drivers in deciding not to drive after drinking as well as to slow or stop their drinking on occasion.

alpha-Thalassemia hydrops fetalis: clinical and ultrasonographic considerations.

Five pregnant Southeast Asian women presenting during a 14-month period with microcytic anemia, preeclampsia, and size-date discrepancies were all ultimately diagnosed as carrying fetuses with homozygous alpha-thalassemia hydrops fetalis. The perinatal complications of this hemoglobin disorder are unique to persons of this ethnic background and include uniform fatality for the affected infant, maternal preeclamptic morbidity, and retained placenta. In this report the obstetric ultrasound findings are presented and the clinical manifestations are discussed, with recommendations made to reduce this emerging public health problem in the United States.

Hydranencephaly: prenatal and neonatal ultrasonographic appearance.

The prenatal diagnosis and postpartum confirmation of hydranencephaly is discussed. The need for an adequate knowledge of fetal cranial anatomy when performing obstetric sonography is stressed.