The effect of raloxifene on markers of bone turnover in older women living in long-term care facilities

OBJECTIVES: To examine the effect of raloxifene on bone turnover in elderly women. DESIGN: Clinical intervention. SETTING: Long-term care facilities. PARTICIPANTS: Nineteen women completed the study, mean age 85 (range 76-99). INTERVENTION: Raloxifene 60 mg was given daily for 12 weeks. MEASUREMENTS: Markers of bone turnover were plasma C-telopeptides of type I collagen (CTx), urine cross-linked N-telopeptides of type I collagen (NTx) and serum tartrate-resistant acid phosphatase (TRAP 5b), plasma osteocalcin, and serum bone alkaline phosphatase. Other markers were serum 25-OH vitamin D, parathyroid hormone, ionized calcium, and phosphate. Markers were measured at baseline, after calcium and vitamin D had been taken for 6 weeks, after raloxifene had been taken for 12 weeks, and 6 weeks after raloxifene had been stopped. Paired sample t test was used to examine changes in markers at each time point. RESULTS: Plasma CTx decreased on average by 31%, urinary NTx by 35%, plasma osteocalcin by 25%, serum bone alkaline phosphatase by 15% (P<.01), and serum TRAP 5b by 10% (P<.05) on treatment. CONCLUSION: Raloxifene reduces bone turnover in elderly women living in long-term care facilities. The effect of raloxifene on bone turnover is comparable with that seen in younger postmenopausal women.     

A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.     

Assessment of Microvascular Abnormalities by Nailfold Capillaroscopy in Juvenile Dermatomyositis After Medium‐ to Long‐Term Followup

Objective

In juvenile dermatomyositis (DM), microvascular abnormalities, measured by nailfold capillaroscopy (NFC), are common early in the disease course. We aimed to compare the presence of NFC abnormalities in patients with medium‐ to long‐term juvenile DM with that of controls, and to explore associations between NFC abnormalities and disease activity and other disease characteristics.

Methods

Fifty‐eight juvenile DM patients with a median disease duration of 16.8 (range 2–38) years were clinically examined and compared with matched controls. By NFC, we assessed nailfold capillary density (NCD), giant capillaries, scleroderma, and neovascular pattern (defined as scleroderma active or late pattern). NFC was analyzed with researchers blinded to patient/control identity and disease characteristics. We measured disease activity and damage by validated tools, and patients were categorized as having active or inactive disease according to the Paediatric Rheumatology International Trials Organisation criteria.

Results

Compared to controls, patients had decreased NCD (mean ± SD 6.4 ± 2.1/mm versus 7.6 ± 0.8/mm; P = 0.001) and showed more abnormality in all other NFC parameters; 36% of patients versus 4% of controls had NCD <6/mm (P < 0.001). Giant capillaries, scleroderma, and neovascular pattern were found in 9%, 84%, and 41% of patients, respectively. Patients with active disease (n = 30) presented more frequently with neovascular pattern than patients with inactive disease (n = 28) (P = 0.041). Decreased NCD and neovascular pattern were associated with higher levels of disease activity and impaired muscle function.

Conclusion

After medium‐ to long‐term followup, juvenile DM patients had decreased NCD and, often, neovascular pattern; both were associated with higher levels of disease activity and impaired muscle function. This suggests that NFC can be a biomarker for disease activity in longstanding juvenile DM too.

     

The VUKA family program: Piloting a family-based psychosocial intervention to promote health and mental health among HIV infected early adolescents in South Africa

An increasing number of adolescents born with HIV in South Africa are on antiretroviral treatment and have to confront complex issues related to coping with a chronic, stigmatizing and transmittable illness. Very few evidence-based mental health and health promotion programs for this population exist in South Africa. This study builds on a previous collaboratively designed and developmentally timed family-based intervention for early adolescents (CHAMP). The study uses community-based participatory approach as part of formative research to evaluate a pilot randomized control trial at two hospitals. The paper reports on the development, feasibility, and acceptability of the VUKA family-based program and its short-term impact on a range of psychosocial variables for HIV + preadolescents and their caregivers. A 10-session intervention of approximately 3-month duration was delivered to 65 preadolescents aged 10–13 years and their families. VUKA participants were noted to improve on all dimensions, including mental health, youth behavior, HIV treatment knowledge, stigma, communication, and adherence to medication. VUKA shows promise as a family-based mental and HIV prevention program for HIV + preadolescents and which could be delivered by trained lay staff.     

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as neutrophils extravasate, and whether surface density of CD11b and CD62L differs between long-term tobacco smokers (LTS) with and without COPD compared with healthy never-smokers (HNS). Unstimulated blood neutrophils from LTS with (n = 5) and without (n = 9) COPD displayed lower surface density of CD62L compared with HNS (n = 8). In addition, surface density of CD11b was higher in bronchoalveolar lavage (BAL) neutrophils from LTS without COPD compared with those with COPD and HNS. Moreover, in BAL neutrophils from all study groups, CD62L was lower compared with matched blood neutrophils. In addition, BAL neutrophils responded with a further decrease in CD62L to ex vivo TNF stimulation. Thus, neutrophils in the airway lumen display a higher state of priming than systemic neutrophils and bear the potential to be further primed by local cytokines even with no smoking or the presence of COPD, findings that may represent a universal host defense mechanism against local bacteria. Moreover, systemic neutrophils are primed in LTS regardless of COPD. Further studies in larger materials are warranted to determine whether the priming of neutrophils is protective against COPD or merely preceding it.