Subsensitivity of beta-adrenoceptor responses in asthmatic patients taking regular low dose inhaled salbutamol

Summary Tremor (Tr), chronotropic (HR) and metabolic (K, Glu) responses to cumulative doses of inhaled salbutamol (100 g to 4000 g) were compared in an age and sex matched group of 7 normal (N) and asthmatic (A) subjects.Comparison of regression lines between groups showed differences in HR and K. This was also reflected in attenuation of maximum responses in group A, for HR and K.These results show subsensitivity of chronotropic and hypokalaemic responses in patients with asthma, which may reflect tachyphylaxis from the effects of long term inhaled salbutamol therapy.     

Olive oil,other dietary fats,and the risk of breast cancer (Italy)

Data from a multicenter case-control study on breast cancer conducted in Italy have been used to analyze the relationship of olive oil and other dietary fats to breast cancer risk. Cases were 2,564 women hospitalized with histologically confirmed, incident breast cancer. Controls were 2,588 women admitted to the same network of hospitals for acute, non-neoplastic, non-hormone related, on-digestive tract disorders. Cases and controls were interviewed between 1991 and 1994 using a validated food-frequency questionnaire. The data were modelled through multiple logistic regression controlling for demographic and reproductive breast-cancer risk factors, energy intake and, mutually, for types of dietary fat. For olive oil, compared with the lowest quintile, the odds ratios (OR) were 1.05, 0.99, 0.93, and 0.87 for increasing quintiles of intake; in a model postulating linear logit increase, the OR per unit (30g) was 0.89 (95 percent confidence interval [CI]=0.81–0.99, P=0.03). Among other oils or fats considered, the OR for the highest level of intake was 0.72 (CI=0.6–0.9) for a group of specific seed oils (including safflower, maize, peanut, and soya) compared with nonusers. The ORs for the highest cf lowest level of intake were 0.80 for mixed or unspecified seed oils, 0.95 for butter, and 0.96 for margarine. The study, based on a large dataset from various Italian regions, shows an inverse relationship of breast cancer risk with intake of olive oil and other vegetable oils, but not with butter or margarine.     

The effect of an applied electric field on macrophage accumulation within the subacute spinal injury

Macrophages are implicated to play a substantive role in the acute inflammatory reaction to CNS insult in the delayed progressive secondary damage to parenchyma, espacially myelin. When placed in an electrical field in vitro, macrophages show directed pseudopodial extensions and migrate towards the positive pole (anode). We have evaluated if ED1 positive macrophage accumulations in rat spinal cord injuries were affected by the applied extracellular voltage, comparing their numbers to a sham treated group. Our hypothesis was that the applied voltage may reduce the concentration of phagocytes in the central injury and thus reduce the level of secondary damage produced by them. The applied voltage gradient did not alter the number or density of macrophage accumulations in the three week lesion, nor is there any difference in the degree of cavitation between control and experimental groups.     

Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II trial.

PURPOSE: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. METHODS: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. RESULTS: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. CONCLUSION: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.     

The cyclooxygenase-2 product prostaglandin E2 modulates cardiac contractile function in adult rat ventricular cardiomyocytes.

Prostaglandin E(2) (PGE(2)), a product of the cyclooxygenase-2 pathway, has been shown to increase cardiac output and modulate cardiac contractile function. However, whether the cardiac contractile response of PGE(2) is due to its action on single ventricular myocytes has not been elucidated. To assess the mechanical effect of PGE(2) at the cellular level, adult rat ventricular myocytes were isolated and stimulated to contract at 0.5Hz. Mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix Myocam analog-to-digital optical detection system. Contractile and intracellular Ca(2+) properties were evaluated as peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening or relengthening (+/-dL/dt) and Ca(2+)-induced intracellular Ca(2+) fluorescence release (CICR), baseline intracellular Ca(2+) levels and intracellular Ca(2+) decay rate (tau). PGE(2) (10(-8) to 10(-3)M) elicited an augmentation in PS but had no effect on TPS, TR(90), +/-dL/dt, CICR and tau. High concentration of PGE(2) (10(-5)M or higher) reduced the baseline intracellular Ca(2+) levels. These data indicate that the myocardial contractile response of PGE(2) may be due to its direct cardiac contractile action at the single ventricular myocyte level, probably through a mechanism independent of intracellular Ca(2+) release.     

Over-the-counter medications containing diphenhydramine and doxylamine used by older adults to improve sleep

International Journal of Clinical Pharmacy - Background The unintentional misuse of over-the-counter sleep aids among older adults is an important public health problem and a focus of Healthy...     

Numerical simulation for a wind dust event in the US/Mexico border region

Soil-derived dust represents one of the major components of the natural atmospheric aerosols. Arid and semiarid areas with unpaved and non-vegetated land cover are particularly vulnerable to windblown dust, which results in high particulate matter pollution. To understand, predict, and mitigate the impact of dust aerosol on air quality and climate, it is necessary to parameterize the emission rate of dust particles from the wind erosion processes accurately. However, windblown dust emission is poorly represented in existing air quality models. In this paper, a windblown dust emission model has been developed based on a parameterization of threshold wind friction velocity depending on the roughness of surface, vegetation type, soil type, soil moisture content, and on the size distribution of aerosols. The proposed dust model incorporates into a region air quality modeling system to simulate a North American dust storm episode occurring near the border of southwestern USA and northwestern region of Mexico on 23 February 2007. It is shown that the implementation of a windblown dust model in an air quality model can significantly improve the model capability for capturing the dust episode. The simulation of the model is in good agreement with the evolution of dust distribution. The modeled dust spatial patterns matched dust cloud patterns appearing on satellite images. Implementation of the windblown dust model successfully captured the time of peak particulate matter (PM) concentrations for both PM₁₀ and PM_2.5, as well as the peak value of the PM_2.5 concentration. The modeled results clearly demonstrate an improved ability to predict PM events by applying the windblown dust emission scheme.