Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues.

The syntheses and biological activities of a number of benzamide derivatives, designed from rolipram, which are selective inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), are described. The effects of changes to the alkoxy groups, amide linkage, and benzamide N-phenyl ring on the inhibition of the cytosolic PDE IV from pig aorta have been investigated. As a result, some highly potent and selective PDE IV inhibitors have been identified.

Inner-city clinics enable a ministry to continue. A Minnesota congregation expands its acute care ministry in order to serve the poor.

In 1991 the St. Paul Province of the Sisters of St. Joseph of Carondelet formed Carondelet LifeCare Ministries (CLM) to ensure that the poor and underserved in the Minneapolis-St.

Fasciocutaneous island flaps for orthopaedic management in lower limb reconstruction using dermatomal precincts.

This paper describes a technique of fasciocutaneous island flaps used in reconstruction of the lower limb. It is very versatile and some 26 individual flaps in 22 patients have been used to reconstruct skeletal and soft tissue problems from the popliteal fossa to the ankle joint. These longitudinally designed flaps made up of a trilaminate of skin, subcutaneous fat and fascia are aligned within the dermatomal precincts.

Epithelioid stromal cells in lymphocytic mastitis--a source of confusion with invasive carcinoma.

Fourteen examples of lymphocytic mastitis (LM) with epithelioid stromal cells characterized by formation of a palpable, hard breast mass composed of a predominantly lobulocentric lymphocytic infiltrate, stromal fibrosis, and an unusual stromal infiltrate of epithelioid cells are presented. The epithelioid cells were so prominent and abundant that the possibility of an infiltrating carcinoma was raised in three cases, and a fourth case was misinterpreted as a granular cell tumor. Interestingly, eight of the 12 women and the only male patient had long standing, insulin dependent diabetes mellitus (IDDM), whereas two had IDDM and hypothyroidism, one had hypothyroidism alone, and one had systemic lupus erythematosus.

Disposition of salicylic acid in malnourished Ethiopian children after single oral dose.

The disposition of salicylic acid and salicyluric acid was studied in 57 Ethiopian children of varying nutritional status after oral administration of sodium salicylate in single doses of either 12.5 or 25 mg/kg. There was no apparent influence of nutritional status on oral salicylate disposition when related to total plasma concentrations.

Hyperphosphataemia after enemas in childhood: prevention and treatment.

The case of a child with severe hyperphosphataemia and symptomatic hypocalcaemia secondary to retention of phosphate administered through an antegrade continence enema is reported. Caution should be exercised with the use of phosphate enemas and prompt action taken to remedy retention. The use of glucose with insulin in the emergency management of acute hyperphosphataemia is discussed.

Decreased chloramphenicol clearance in malnourished Ethiopian children.

The disposition of chloramphenicol and chloramphenicol monosuccinate has been studied in thirty-four Ethiopian children of varying nutritional status. After a single intravenous dose corresponding to chloramphenicol 25 mg per kg bodyweight, the plasma clearance of chloramphenicol monosuccinate was decreased only in severely malnourished children with kwashiorkor. Seventeen % of the dose (range 0-51%) was recovered in urine as intact prodrug, indicating incomplete and variable bioavailability of chloramphenicol.

Acyl-CoA:cholesterol O-acyl transferase (ACAT) inhibitors. 1. 2-(Alkylthio)-4,5-diphenyl-1H-imidazoles as potent inhibitors of ACAT.

A potent, bioavailable ACAT inhibitor may have beneficial effects in the treatment of atherosclerosis by (i) reducing the absorption of dietary cholesterol, (ii) reducing the secretion of very low density lipoproteins into plasma from the liver, and (iii) preventing the transformation of arterial macrophages into foam cells. We have found that a mevalonate derivative 2, which contains a 4,5-diphenyl-1H-imidazol-2-yl moiety, inhibits rat hepatic microsomal ACAT in vitro and produces a significant hypocholesterolemic effect in the cholesterol-fed rat. Structure-activity relationships for analogues of 2 demonstrate that the 4,5-diphenyl-1H-imidazole moiety is a pharmacophore for inhibition of rat microsomal ACAT.

The effect of artemisinine, its derivatives and mefloquine against chloroquine-resistant strains of Plasmodium falciparum in vitro.

A 48 h in vitro test of the efficacy of artemisinine, dihydroartemisinine, artemether, mefloquine and chloroquine was carried out against 3 chloroquine-resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India. A sigmoid Emax model was fitted to all in vitro inhibition data for each combination of drug and strain. Strains K1 and LS21 were strongly resistant to chloroquine, whereas T996 was partially resistant.

Turnover of exogenous artificial surfactant.

The turnover of the artificial surfactant Exosurf after its administration to infants with respiratory distress syndrome was studied. High performance liquid chromatography was used to compare the phosphatidylcholine (PC) composition of serial endotracheal tube secretions from three groups of infants. There were 22 infants who received two doses of Exosurf in 24 hours (group 1), 10 infants who received four doses in 36 hours (group 2), and 41 control infants who did not receive Exosurf.

Phosphatidylcholine composition of endotracheal tube aspirates of neonates and subsequent respiratory disease.

The phosphatidylcholine (PC) content of the initial endotracheal tube aspirate was measured in 105 infants intubated for resuscitation or for ventilation for respiratory distress syndrome, using high performance liquid chromatography and postcolumn fluorescence derivitization with diphenyl-1,3,5-hexatriene. Sixty eight had measurable PC. Of the infants who developed respiratory distress syndrome, with or without subsequent chronic lung disease, neither the percentage of dipalmitoylphosphatidylcholine (DPPC) nor the ratio of DPPC to palmitoyloleoylphosphatidylcholine (POPC), showed any correlation with gestational age.

Immunocytochemical localization of FMRFamide in the central nervous system and the kidney of Helisoma duryi (Mollusca): its possible antidiuretic role.

The distribution of FMRFamide-immunoreactive neurons in the central nervous system of the freshwater pulmonate, Helisoma duryi is described. All parts of the central nervous system except the two pleural and the right parietal ganglia, contain immunoreactive neurons. By immunogold techniques, only one kind of neurosecretory FMRFamide-immunoreactive cell (previously identified as the type-3 cell) was localized in the visceral and left parietal ganglia.

Suspected cycad (Cycas revoluta) intoxication in dogs.

Three dogs which ingested part of the stem of a Japanese cycad (Cycas revoluta) vomited repeatedly within hours after ingestion, showed marked depression, severely congested mucous membranes, increased thirst and profuse salivation. Subsequent hematological and blood chemical investigation revealed elevated serum concentrations of alanine transaminase, an initial mild lymphocytopenia, thrombocytopenia and a leucocytosis. The dogs recovered uneventfully.

Cell size of mammalian myocardia is not related to physiological demand.

Morphological characteristics of myocardial ventricular myocytes have been evaluated from 5 mammalian orders with resting heart rates ranging from 51 to 475 bpm. The purpose was to determine if morphological characteristics of the myocardia are related to the functional demand imposed on the cell as represented by the resting heart rate. Cell size is a constant among mammals of different sizes which have different physiological demands.

Antisperm antibody detection using concurrent cytofluorometry and indirect immunofluorescence microscopy.

Anti-sperm antibodies from serum and seminal plasma were detected by concurrent flow cytometry and epifluorescence microscopy using fluorescein-conjugated antihuman immunoglobulins. Experimental conditions were designed, taking advantage of several monoclonal antisperm antibodies, to test aspects of the assay before clinical application. Perturbation of membrane integrity altered both the localization of binding and the number of sperm cells positive for bound antibodies.

In vitro activity of artemisinin, its derivatives, and pyronaridine against different strains of Plasmodium falciparum.

The activities of artemisinin (qinghaosu), dihydroartemisinin (dihydroqinghaosu), artemether and pyronaridine were tested in a 48 h in vitro assay against 3 chloroquine-sensitive and one chloroquine-resistant strains of Plasmodium falciparum. Growth inhibition was modelled with a sigmoid Emax model. All compounds markedly inhibited the growth of all strains although, for the chloroquine-resistant strain, merozoites were detected at concentrations as high as 10(-4) M of artemisinin, dihydroartemisinin and artemether.

The increase in lipid peroxidation in diabetic rat lens can be reversed by oral sorbinil.

Malondialdehyde (MDA), a product of lipid peroxidation, was measured in the lens of rats in which diabetes had been induced by treatment with streptozotocin (85 mg/kg). The MDA level increases nearly 100% in lenses from diabetic rats, compared with lenses from age-matched control rats. Treating rats with insulin decreases the MDA content of the diabetic rat lens to normal levels.

Prospective study of concurrent ploidy analysis and routine cytopathology in body cavity fluids.

A total of 390 body cavity fluids were analyzed by both cytopathologic examination and flow cytometric DNA analysis. The two methods gave compatible results in analyses of 304 fluids (78%). In 24 patients, cytopathologic studies found the specimens to contain malignant cells, but the DNA content was diploid.

Changes in the fine structure of the endocrine dorsal body cells of Helisoma duryi (mollusca) induced by mating.

The morphology and the organization of the endocrine dorsal bodies (DB) of non-reproducing virgin and castrated, and reproducing mated Helisoma duryi have been examined using serial sectioning. The DB cells occur in two masses on the mid-dorsal side of the cerebral commissure, each of which has a cortical zone containing the cell bodies and a medulla where cell processes terminate. The cell bodies measure 10-15 μm in diameter, and are arranged in lobules of 6-12 cells.