Perceived control of asthma and quality of life among adults with asthma.

BACKGROUND: Perceived control of certain chronic conditions influences health status outcomes. OBJECTIVE: To explore the impact of perceived control of asthma on asthma-specific and generic health status outcomes among adults with asthma. Perceived control was defined as individuals' perceptions of their ability to deal with asthma and its exacerbations. METHODS: Data were drawn from the baseline and first two followups of a longitudinal study of adults with asthma surveyed by telephone at 18-month intervals. An 11-item questionnaire (Perceived Control of Asthma Questionnaire [PCAQ]) was developed and validated. RESULTS: The PCAQ demonstrated high internal consistency (Cronbach's alpha = 0.79). Greater perceived control was associated with less severe asthma, greater asthma self-efficacy, lower perceived asthma severity, lower perceived danger from asthma, and greater perceived usefulness of asthma medicines. Greater perceived control was significantly associated with better asthma-specific quality of life concurrently and 18 and 36 months later, after controlling for demographics, smoking, and severity of asthma. Greater perceived control as also significantly associated with generic mental health outcomes concurrently and 18 and 36 months later, after controlling for covariates. Perceived control was associated with physical function concurrently and 18 months later, but not 36 months later. CONCLUSIONS: The PCAQ is a reliable and valid measure of perceived control of asthma. Perceived control of asthma was associated with both asthma-specific and generic health status outcomes, concurrently and predictively. If perceived control could be modified, better outcomes, particularly better psychologic outcomes, might be achieved for individuals with asthma.     

Regional differences in calcium-release channels from heart.

The heart is a heterogeneous tissue composed of several cell types tailored for specialized functions. We found that intracellular channels also exhibit regional specialization. In cardiac and skeletal muscle these channels are called the calcium-release channel and are identified by activation with either calcium or caffeine and inhibition by the hexavalent cation ruthenium red. The calcium-release channel of the sarcoplasmic reticulum from the interventricular septum has a smaller conductance (31 pS vs. 100 pS) and has longer open and closed times when compared with the channel from left-ventricular free wall. An additional calcium-permeable channel with an even smaller conductance (17 pS) was found in the septum, and this channel is similar to the inositol 1,4,5-trisphosphate-gated channel from smooth muscle and different from the calcium-release channel (ryanodine receptor) from skeletal and cardiac muscle. The inositol 1,4,5-trisphosphate-activated channel may be derived from specialized conducting tissue that is relatively abundant in the septum, whereas the other calcium-release channels may be derived from regionally specialized myocardial cells in the septum and free wall.     

Protective Effect of Oral Acetylcysteine against the Hepatorenal Toxicity of Carbon Tetrachloride Potentiated by Ethyl Alcohol

Considering the well-documented protection of acetylcysteine (AC) in hepatotoxicity related to acetaminophen, we studied the preventive potential of AC against mild hepatotoxicity of CCl4, potentiated with ethyl alcohol (ETH) and the role of tissue glutathione. Rats fed a liquid diet with 30% of energy from ETH, had-intraperitoneal CCl4 administered in three injections, at 7-day intervals. AC was ingested at the level for acetaminophen overdose. ETH markedly potentiated the injury induced by CCl4, as evidenced by higher values of serum alanine aminotransferase (ALT), urinary bile acids (BA), serum creatinine, histological score of liver cell necrosis, mortality and by lower body weights and lower liver glutathione, when compared with CCl4 alone. Protective effect of AC consisted of a lesser hepatocytic necrosis, better body weights and higher liver glutathione. We conclude, that AC favorably modifies liver damage induced by CCl4 and potentiated with ETH. There is a preventive role for AC in subjects who combine ETH overuse with exposure to hepatotoxic xenobiotics, whose toxicity is modified by tissue glutathione.     

Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone.

Evidence exists that a norepinephrine/prostaglandin E2 (PGE2)/cAMP pathway is involved in the regulation of luteinizing hormone-releasing hormone (LHRH) secretion. The aim of the present experiments was to determine if release of LHRH from the immature rat hypothalamus could also be stimulated by activation of protein kinase C. Median eminences from 28-day-old female rats were incubated in vitro with either dioctanoylglycerol (a synthetic diacylglycerol that selectively activates protein kinase C in intact cells) or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (another protein kinase C activator). Both agents increased LHRH release, the response to dioctanoylglycerol being more pronounced than that to the phorbol ester. This direct activation of protein kinase C was not accompanied by changes in PGE2 formation. Activation of the PGE2/cAMP pathway by either norepinephrine, PGE2, or forskolin (a stimulator of adenylate cyclase) increased LHRH release. Dioctanoylglycerol or phorbol ester in conjunction with either norepinephrine, PGE2 or forskolin resulted in an additive effect on LHRH release suggesting coexistence of both pathways. Phospholipase C, which activates protein kinase C via formation of diacylglycerol, increased the release of both LHRH and PGE2. This suggests that an increase in endogenous phospholipase C activity caused by neurotransmitter inputs may lead to both activation of protein kinase C and PGE2 formation. Blockade of cyclooxygenase activity by indomethacin obliterated phospholipase C-induced PGE2 release. The same treatment reduced the LHRH response by only 50% indicating that protein kinase C activation can cause LHRH release in the absence of PGE2 synthesis. It is suggested that the median eminence of the rat possesses a protein kinase C-dependent pathway that is coupled positively to LHRH release and complements PGE2/cAMP-dependent mechanisms. Norepinephrine, however, does not appear to be the neurotransmitter responsible for activating the protein kinase C pathway. Simultaneous activation of both pathways may provide a mechanism by which a large increase in LHRH secretion occurs, such as in the afternoon of first proestrus.     

Measurement of end-capillary PO2 with positron emission tomography

The analysis of positron emission tomography measurements of oxygen metabolism has been extended to provide a quantitative estimate of end-capillary PO2. The principle of this extension rests on the idea that the oxygen extraction fraction can be used to calculate the end-capillary oxygen saturation of the blood. The relation between oxygen saturation and PO2 is obtained through the oxygen dissociation curve. Our studies show that in addition to the local oxygen extraction fraction, arterial PO2 and pH values are needed in the calculation, whereas fairly large variations in factors such as PCO2, hematocrit, hemoglobin, and plasma protein levels have little or no effect. Rough estimates of end-capillary PO2 can be made using standard O2 dissociation nomograms. Blood gas and acid-base properties of blood have been known for decades, making it possible to account accurately for individual differences that may be encountered when studying patients. Measurements in nine normal subjects yielded a mean end-capillary PO2 value of 31.2 mm Hg. The ability to make a quantitative visualization of altered patterns of end-capillary PO2 provides an additional dimension to the investigation of stroke disease and tumor metabolism.     

Fiber Matrix Descriptors from Permeability Data Without Requiring Membrane Thickness: Theory,Results, and Optimization

Objective: Permeability of basement membrane and all other barriers contains a term for membrane thickness (Δx). This naturally leads to development of methods for measuring Δx that are imprecise, inaccurate, expensive, subject to preparation artifact, and inattentive to variability. Although height and shape of permeability (P) vs. probe radius (α) curves are sensitive to Δx, ln(P) or ln(P/free diffusivity or D_o) curves have shapes independent of Δx. It should, thus, be possible using such characteristics to determine fiber radius (r_f) and void volume ratio (ε) without Δx. We developed such a method to derive membrane structure by the standard model of Ogston and present its experimental evaluation. Methods: Basement membranes were self-assembled using 1: 1 Matrigel: 0.01 M Tris/150 mM NaCl/1.0 mM CaCl₂ buffer on 0.4-μ polycarbonate supports with transport measured in diffusion chambers using FITC-labeled hydroxyethyl starch probes from 25 to 102 Å in radius. Sampling was at 0.5 hr and then for each hour up to 5. Other membranes were measured 7 days after formation. Results: The best fit of the new technique occurred at 3 hr with R² = 0.949 ± 0.003 SEM, r_f = 36.8 ± 2.4 Å, and ε = 0.87 ± 0.02. Membranes studied for 7 days showed more variability but essentially the same characteristics. Conclusions: Membrane thickness is not necessary to reduce permeability of basement membrane to structure, and optimum sampling time is 3 hr.     

Benign familial leukopenia and neutropenia in different ethnic groups

Benign hereditary leukopenia-neutropenia has been reported in several ethnic groups, including Yemenite Jews, Blacks of South African extraction, West Indians and Arab Jordanians. The subjects with BFL were shown not to have an increased incidence of infections, and their response to infection did not differ from subjects having normal white blood cell counts. This study entails the report of two additional unrelated ethnic groups with familial neutropenia - Black Beduin and Falashah Jews. The familial nature of the phenomenon was confirmed. The suggested mechanism of this type of neutropenia is a defect in release of mature WBC from the bone marrow to the peripheral circulation. All ethnic groups thus far reported have tanned or dark skin. The significance of this common feature has still to be elucidated.