Effects of disease and corticosteroids on appendicular bone mass in postmenopausal women with rheumatoid arthritis: comparison with axial measurements

The potential value of measurements of peripheral bone mass in rheumatoid arthritis (RA) as an assessment of long-term disease activity has recently received renewed attention. This study examines the effects of RA and corticosteroid therapy on newer methods of measuring peripheral bone mass, comparing the results with dual-energy X-ray absorptiometry (DXA) at axial sites. Peripheral quantitative computed tomography of the radius, ultrasound of the calcaneus, and DXA of the hip and spine were compared between 29 controls and 46 women with RA of whom 25 were receiving low-dose corticosteroid therapy. Bone mass was significantly reduced in the RA groups for: (i) radial trabecular (36.1%) and total (15.6%) measurement sites; (ii) calcaneal ultrasound attenuation (31.7%) and velocity (6.6%); and (iii) femoral neck (15.4%) bone mineral density. Lumbar spine and radial cortical measurements were not significantly affected. There were no significant differences between the RA groups. Disease activity and physical activity did appear to be responsible for much of the reduction in bone mass. These results demonstrate that RA is associated with significant bone loss at the hip, radius and calcaneus, but not at the lumbar spine. In this small study, low-dose corticosteroids had little additional deleterious effect.      

Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.     

Drugs affecting HbA1c levels

Glycated hemoglobin (HbA1c) is an important indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. However, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Important among these is the use of certain non-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately raise or lower the HbA1c levels, and the postulated mechanisms for the same.     

Fine aerosol and PAH carcinogenicity estimation in outdoor environment of Mumbai City, India

Exposure to fine particles has been shown to cause severe human health impacts. In the present study, outdoor fine particles as well as elemental and organic carbon concentrations were measured in four locations within Mumbai city, India, during 2007–2008. The average outdoor PM_2.5 mass concentrations at control, kerb, residential and industrial sites were 69 ± 21, 84 ± 32, 89 ± 34, 95 ± 36 μg/m³. In addition, fine particle PAHs were measured during the post monsoon season. The sum of PAHs in PM_2.5 at same above four sites were 35.27 ± 2.10, 42.96 ± 2.49, 175.76 ± 8.95 and 90.78 ± 4.74 ng/m³, respectively. Estimating the carcinogenic potential of PAHs with equivalents of Benzo(a)pyrene (BaPE). The maximum value of BaPE (18.8) was reported in the residential site. A trend of lung cancer cases in Mumbai city is also presented. This was a preliminary study in understanding the health effects of PAHs in Mumbai city.     

Monitoring antimalarial drug resistance in India via sentinel sites: outcomes and risk factors for treatment failure, 2009–2010

Objective

To describe India’s National Antimalarial Drug Resistance Monitoring System, measure the efficacy of first-line malaria treatments, and determine risk factors for treatment failure.

Methods

In 2009–2010, prospective studies with 28 days of follow-up were conducted at 25 sentinel sites. Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine (AS+SP); those infected with P. vivax were given chloroquine. Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure. Isolates of P. falciparum were checked for dhfr and dhps mutations.

Findings

Overall, 1664 patients were enrolled. Kaplan–Meier survival analysis showed an efficacy of 98.8% for AS+SP. Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation, but six, including four with treatment failure, remained parasitaemic after 72 hours. Double mutants in dhfr were found in 68.4% of the genotyped isolates. Triple or quadruple mutants in dhfr and mutations in dhps were rare. A daily dose of artesunate of < 3 mg per kg of body weight, age of less than 5 years, and fever at enrolment were associated with an increased risk of treatment failure. Chloroquine remained 100% efficacious and generally cleared P. vivax parasitaemias within 48 hours. Vomiting (seen in 47 patients) was the most common adverse event.

Conclusion

India’s National Antimalarial Drug Resistance Monitoring System provides wide coverage. The first-line antimalarials used in the country remain safe and efficacious. The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration.     

国产尼莫地平片和尼莫通片的生物利用度比较

国产尼莫地平片和尼莫通片的生物利用度比较施孝金王宏图韦阳张静华张莉莉钟明康（上海医科大学华山医院临床药学研究室，上海２０００４０）钙离子通道拮抗剂尼莫地平（ｎｉｍｏｄｉｐｉｎｅ，ＮＭ），临床上主要用于治疗有明显症状的老年性脑功能损伤和由于蛛网膜下腔出...     

Higher Intake of Dairy Is Associated with Lower Cardiometabolic Risks and Metabolic Syndrome in Asian Indians

There is conflicting evidence about the association between dairy products and cardiometabolic risk (CMR). We aimed to assess the association of total dairy intake with CMR factors and to investigate the association of unfermented and fermented dairy intake with CMR in Asian Indians who are known to have greater susceptibility to type 2 diabetes and cardiovascular diseases compared to white Europeans. The study comprised 1033 Asian Indian adults with normal glucose tolerance chosen from the Chennai Urban Rural Epidemiological Study (CURES). Dietary intake was assessed using a validated open-ended semi-quantitative food frequency questionnaire. Metabolic syndrome (MS) was diagnosed based on the new harmonising criteria using central obesity, dyslipidaemia [low high-density lipoprotein cholesterol (HDL) and increased serum triglycerides (TG)], hypertension and glucose intolerance. Increased consumption of dairy (≥5 cups per day of total, ≥4 cups per day of unfermented or ≥2 cups per day of fermented dairy) was associated with a lower risk of high fasting plasma glucose (FPG) [hazards ratio (HR), 95% confidence interval (CI): 0.68, 0.48–0.96 for total dairy; 0.57, 0.34–0.94 for unfermented dairy; and 0.64, 0.46–0.90 for fermented dairy; p < 0.05 for all] compared to a low dairy intake (≤1.4 cups per day of total dairy; ≤1 cup per day of unfermented dairy; and ≤0.1 cup per day of fermented dairy). A total dairy intake of ≥5 cups per day was also protective against high blood pressure (BP) (HR: 0.65, 95% CI: 0.43–0.99, p < 0.05), low HDL (HR: 0.63, 95% CI: 0.43–0.92, p < 0.05) and MS (HR: 0.71, 95% CI: 0.51–0.98, p < 0.05) compared to an intake of ≤1.4 cups per day. A high unfermented dairy intake (≥4 cups per day) was also associated with a lower risk of high body mass index (BMI) (HR: 0.52, 95% CI: 0.31–0.88, p < 0.05) compared to a low intake (≤1 cup per day), while a reduced risk of MS was observed with a fermented dairy intake of ≥2 cups per day (HR: 0.71, 95% CI: 0.51–0.98, p < 0.05) compared to an intake of ≤0.1 cup per day. In summary, increased consumption of dairy was associated with a lower risk of MS and components of CMR.