The Middle-Out Perspective: an approach to formalise 'normal practice' in public health advocacy.

AIMS: The middle-out perspective (MOP) provides a lens to examine how actors positioned between government (top) and individuals (bottom) act to promote broader societal changes from the middle-out (rather than the top-down or bottom-up). The MOP has been used in recent years in the fields of energy, climate change, and development studies. We argue that public health practitioners involved with advocacy activities and creating alliances to amplify health promotion actions will be familiar with the general MOP concept if not the formal name. The article aims to demonstrate this argument. METHODS: This article introduces the MOP conceptual framework and customises it for a public health audience by positioning it among existing concepts and theories for actions within public health. Using two UK case studies (increasing signalised crossing times for pedestrians and the campaign for smoke-free legislation), we illustrate who middle actors are and what they can do to result in better public health outcomes. RESULTS: These case studies show that involving a wider range of middle actors, including those not traditionally involved in improving the public's health, can broaden the range and reach of organisations and individuals involving in advocating for public health measures. They also demonstrate that middle actors are not neutral. They can be recruited to improve public health outcomes, but they may also be exploited by commercial interests to block healthy policies or even promote a health-diminishing agenda. CONCLUSION: Using the MOP as a formal approach can help public health organisations and practitioners consider potential 'allies' from outside traditional health-related bodies or professions. Formal mapping can expand the range of who are considered potential middle actors for a particular public health issue. By applying the MOP, public health organisations and staff can enlist the additional leverage that is brought to bear by involving additional middle actors in improving the public's health.

Effect of standardized post-coercion review on subjective coercion: Results of a randomized-controlled trial.

BACKGROUND: Post-coercion review has been increasingly regarded as a useful intervention in psychiatric inpatient setting. However, little is known about its effect on perceived coercion. METHODS: A multicenter, two-armed, randomized controlled trial was conducted, aiming at analyzing the effect of post-coercion review on perceived coercion. People with severe mental disorders, who experienced at least one coercive measure during inpatient treatment, were randomized using Zelen's design to an intervention group receiving standardized post-coercion review, or a control group treated as usual. The MacArthur admission experience scale (AES) and the coercion ladder (CL) were used to assess perceived coercion during inpatient treatment. The coercion experience scale (CES) measured experienced coercion during the coercive intervention. Analyses of covariance were performed to determine group differences. RESULTS: Of 422 randomized participants, n = 109 consented to participate in the trial. A restricted intention-to-treat analysis of all individuals who consented revealed no significant effect of the intervention on perceived coercion. A significant interaction effect between the factors gender and intervention on the AES scores was found. Sensitivity analysis revealed significant effects of the intervention on both AES and CL scores and an interaction effect between intervention and gender, indicating a higher efficacy in women. No effect of the intervention on CES scores was found. CONCLUSIONS: Standardized post-coercion review sessions did not alleviate the subjective perception of coercion in the total sample. However, post hoc analysis revealed a significant effect of the intervention in women. Results indicate the need to further address gender-specific issues related to coercion.

Induction of mitotic crossing-over in diploid strains of Aspergillus nidulans using low-dose X-rays.

As a contribution towards detecting the genetic effects of low doses of genotoxic physical agents, this paper deals with the consequences of low-dose X-rays in the Aspergillus nidulans genome. The irradiation doses studied were those commonly used in dental clinics (1-5 cGy). Even very low doses promoted increased mitotic crossing-over frequencies in diploid strains heterozygous for several genetic markers including the ones involved in DNA repair and recombination mechanisms. Genetic markers of several heterozygous strains were individually analyzed disclosing that some markers were especially sensitive to the treatments. These markers should be chosen as bio-indicators in the homozygotization index assay to better detect the recombinogenic/carcinogenic genomic effects of low-dose X-rays.

Effect of fatty acid modification on prostacyclin production by cultured human endothelial cells.

We have investigated whether changes in cellular fatty acid saturation can influence prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells. As compared to control cells, those enriched with linoleic acid released 60--75% less PGI2 in response to thrombin or the calcium ionophore A23187. A similar but considerably smaller effect was observed when the cells were enriched with oleic or linolenic acid, but no reduction occurred with palmitic or linoelaidic acids. Some reduction in PGI2 release was noted as early as 1 h after exposure to linoleic acid. When the culture medium was supplemented with linoleic acid, the cell phospholipids contained four to five times more linoleate and 25--40% less arachidonate. These changes were most marked in the choline and serine plus inositol phosphoglyceride fractions. When the fatty acid composition of the cells enriched with linoleic acid was allowed to revert, there was a progressive increase in the capacity of the cells to release PGI2 in response to thrombin. The increase correlated with a reduction in linoleate content of the cell lipids, but there was no change in arachidonate content. This suggests that linoleic acid may act as an inhibitor of PGI2 production. The cultured endothelial cells were also able to produce PGI2 directly from added arachidonic acid. As the arachidonic acid concentration of the medium was raised, PGI2 formation by the linoleate-enriched cells increased relative to control cells, suggesting that the inhibition produced by linoleic acid may be competitive.

Prostaglandin production by 3T3-L1 cells in culture.

Rapidly growing cultures of 3T3-L1 preadipocytes produce large quantities of prostaglandins when they are either stimulated with the calcium ionophore A23187 or incubated with arachidonic acid. The main prostaglandin produced under all conditions was prostaglandin E2. Prostaglandin production in response to ionophore stimulation or incubation with arachidonic acid decreased markedly, however, as the cultures approached confluence, were maintained in the confluent state, or were stimulated to differentiate. Enrichment of confluent, differentiated cultures with arachidonic acid did not enhance prostaglandin production. Recovery of prostaglandin production occurred when logarithmic growth was reinstituted by reseeding confluent cultures at low cell densities, but sparse cultures maintained in a low-growth phase did not recover the ability to produce large amounts of prostaglandin E2. Therefore, the decline in prostaglandin synthetic capacity appears to be associated with the decrease in growth rate as the cells approach confluence. Media conditioned by confluent cells reduced prostaglandin E2 production when added to rapidly growing cells, suggesting that an inhibitor of prostaglandin synthesis may be formed by the confluent cultures. Nondifferentiating 3T3 fibroblasts, which similarly release mainly prostaglandin E2, also exhibited a decrease in prostaglandin production as the cultures became confluent. The amounts of prostaglandins produced by 3T3 cells in the confluent state were much greater, however, than those produced by confluent or differentiated 3T3-L1 cultures. These findings suggest that the low capacity to produce prostaglandins may be involved in either the induction or maintenance of differentiation in 3T3-L1 cells.

Age-related deficits of central muscarinic cholinergic receptor function in the mouse: partial restoration by chronic piracetam treatment.

The effect of aging on muscarinic cholinergic receptor function in dissociated cell aggregates of the mouse brain was investigated using two biochemical models, i.e., carbachol-induced accumulation of inositol monophosphates and carbachol-induced desensitization of muscarinic cholinergic receptors as measured by the sequestration of specific 3H-N-methyl-scopolamine binding. While aging strongly reduced carbachol-induced inositol monophosphate accumulation, desensitization was not affected in the brains of aged animals. Chronic treatment of aged mice with the nootropic drug piracetam (500 mg/kg daily PO) significantly elevated the agonist-induced accumulation of inositol monophosphates possibly by increasing the available number of muscarinic cholinergic receptors not being in a desensitized state. The results support the hypothesis that nootropics like piracetam might act in part by restoring age-related deficits of central muscarinic cholinergic receptor function.

In vitro down-regulation predicts agonist efficacy at central muscarinic cholinergic receptors.

Agonist induced short-term down-regulation of central muscarinic cholinergic receptors in mechanically dissociated cells of the mouse brain has been shown to predict the efficacy of agonists at muscarinic receptors. Pretreatment of cells with full agonists such as carbachol or oxotremorine M resulted in a loss of available muscarinic cholinergic receptors of about 30% using [3H]N-methylscopolamine [( 3H]NMS) as radioligand, whereas a second group of agonists e.g. RS 86 were only weakly active in this regard producing a significantly smaller loss of cell surface muscarinic cholinergic receptors. The magnitude of down-regulation of muscarinic receptors induced by pretreatment with several cholinergic drugs correlates fairly well with their ability to stimulate the phosphatidylinositol turnover. It seems that the agonist induced down-regulation of muscarinic cholinergic receptors on mechanically dissociated neurons of the mouse brain is a simple screening method to test for centrally acting cholinergic agonists.

Therapeutic concentrations of lithium and carbamazepine inhibit cGMP accumulation in human lymphocytes. A clinical model for a possible common mechanism of action?

Although a large variety of biochemical effects have been reported for lithium (Li) and carbamazepine (Cbm), the final molecular mechanism underlying their therapeutic efficacy for recurrent affective disorders is still unknown. The data presented here clearly indicate that therapeutic concentrations of both drugs inhibit sodium nitroprusside-induced accumulation of cGMP in human lymphocytes to about the same extent. The effect is not seen for other antidepressants, and shows pronounced interindividual variations in healthy volunteers. A similar effect of lithium and carbamazepine can also be demonstrated for the cGMP accumulation of central neurons using the model of dissociated cells of the mouse brain. The results are discussed in view of a common mechanism of action of both drugs. Furthermore, it is speculated that the individual sensitivity of the cGMP generating system of human lymphocytes to both drugs might be used to predict therapeutic response or nonresponse of the individual patient.

L- and D-S-nitroso-beta,beta-dimethylcysteine differentially increase cGMP in cultured vascular smooth muscle cells.

We examined the effects of the L- and D-isomers of S-nitroso-beta,beta-dimethylcysteine (L- and D-S-nitrosopenicillamine, 10(-7)-10(-5) M) on the guanosine 3',5'-cyclic monophosphate (cGMP) content of cultured porcine aortic smooth muscle cells and the decomposition of these stereoisomers to nitric oxide (NO). L-S-nitrosopenicillamine was a more potent generator of cGMP than D-S-nitrosopenicillamine although both stereoisomers equally decomposed to NO. The 10(-7) M concentration of L- or D-S-nitrosopenicillamine did not generate detectable amounts of NO although 10(-7) M L-S-nitrosopenicillamine but not D-S-nitrosopenicillamine generated significant amounts of cGMP. This study shows that the stereoisomeric configuration of S-nitrosopenicillamine is an important factor in its biological potency. The data suggest that the extracellular or intracellular generation of NO is not the only mechanism by which this S-nitrosothiol generates cGMP in vascular smooth muscle.

Functional and ultrastructural effects of essential fatty acid deficiency in kidney epithelial cells.

Madin-Darby canine kidney (MDCK) epithelial cells were grown in culture medium supplemented with 1% fetal bovine serum (FBS) to provide a cell culture model of essential fatty acid deficiency (EFAD). 5,8,11-Eicosatrienoic acid (20:3n-9) accumulated in cellular phospholipids, and arachidonic acid (20:4) decreased. A large increase in cellular cholesterol/phospholipid ratio was observed. Hemicyst formation was greatly reduced from normal levels in the EFAD-MDCK cells. Scanning and transmission electron microscopy revealed that EFAD-MDCK were much flatter than their normal counterparts. They had much less dense surface microvilli, mitochondria and other organelles were very sparse, except in the perinuclear area, and much of the peripheral cytoplasm was amorphous. The EFAD was rapidly reversed by the addition of as little as 10 microM linoleic or arachidonic acid to the medium. Cells supplemented with 10% FBS, the usual culture condition, displayed borderline EFAD, with intermediate levels of 20:3n-9 and 20:4 and hemicyst formation. These studies suggest that EFAD reduces water and electrolyte transport in renal tubular epithelium.

[Horton's disease in the course of chronic hepatitis C]. / Maladie de Horton au cours d'une hépatite C chronique.

BACKGROUND: Vascularitis is a well-known extrahepatic manifestation of chronic hepatitis C. Mixed cryoglobulinemia is the most common form. To our knowledge, the present case is the first report associating chronic hepatitis C and temporal arteritis. CASE REPORT: A 56-year-old man with chronic hepatitis C in the precirrhogenic phase presented with fever and weight loss. The patient complained of pain of the scapular and pelvic girdles and headache and physical examination revealed claudication of the jaw and abolition of the upper limb pulses. Biopsy of the temporal artery confirmed the diagnosis of Horton's disease. The patient also had bilateral stenosis of the sub-clavian arteries. DISCUSSION: This observation of Horton's disease involving large vessels in a patient with chronic hepatitis C suggests that an infectious factor might trigger vascularitis.

Modification of col shape and interproximal area after periodontal surgery associated with the restorative alveolar interface (RAI) technique. Histological study in dogs.

The modification of the col shape and position by the restorative alveolar interface technique (RAI) was studied in the interproximal areas between the mandibular first molars and fourth premolars of 10 dogs. Full thickness flaps were raised to expose the interproximal root surface and alveolar bone crest. The RAI procedure was performed only on the experimental sides and the control areas were the opposite side of the same animal. The animals were sacrificed at zero hour, 7, 14, 21 and 28 days for histological analyses. Approximately 6.0-micron-thick sections were made in buccolingual and mesiodistal directions and stained with hematoxylin-eosin and Mallory for light microscopy analysis. A satisfactory healing process was observed up to the 14th and 21st days which showed a modified col shape. At this time, an inflammatory reaction developed affecting the evolution of the healing. The surgery had probably created conditions for the installation of an inflammatory process resulting from the modified anatomy of the interdental area.