Psoriatic osteopathy--results of histomorphometric studies

In 23 patients with psoriatic arthritis and 9 patients with psoriasis without joint involvement, we took bone biopsies from the iliac crest. Histomorphometrical investigations showed that the volume density of the bone was not decreased in either group of patients, but we found a high rate of turnover remodelling. An elevated rate of bone turnover is regarded as the characteristic principle of "psoriatic osteopathy", which--more exactly--should be called "latent osteopathy". Deficiency of vitamin D is discussed as a possible etiological factor.     

Pattern electroretinogram and visual evoked potential amplitudes are influenced by different stimulus field sizes and scotomata

The pattern electroretinogram and the visual evoked potential were recorded simultaneously with various stimulus fields and artificial scotomata of increasing sizes. In contrast to an earlier study, a smaller check size (20) and two stimulus field sizes (20° × 20° and 10° × 10°) for the scotomata were used. With a concentric decreasing stimulus field, a reduction of both the pattern electroretinogram and visual evoked potential was found. Both showed a simultaneous reduction of amplitudes, but, compared with the amplitude in the full field, the reduction was more extensive for the pattern electroretinogram at each test field size. This implies a greater contribution to the pattern electroretinogram from more eccentric retinal parts. An artificial central scotoma of increasing size in the 20° × 20° field had less influence on the pattern electroretinogram than on the visual evoked potential. The percentage amplitude loss of the visual evoked potential was more pronounced. The visual evoked potential was eventually abolished by a scotoma size from 10° × 10° upward, while the pattern electroretinogram was still registrable. When scotomata of similar size were introduced in a smaller (10° × 10°) field, percentage pattern electroretinogram and visual evoked potential amplitude losses were less separated than in a larger (20° × 20°) test field.     

Evaluation of nutritional counselling in HIV-associated malnutrition

In HIV-infected patients, the outcome of counselling as the first step of a nutritional intervention programme was evaluated, in order to identify clinical and nutritional predictors for its efficacy. 75 HIV-infected patients were investigated, most with advanced disease. Nutritional status was determined by body weight, bioelectrical impedance and 7-day food intake record. Prior mean weight loss was 10% (range = +4% to -31%). Counselling facilitated weight gain in 40 75 patients (1-4 months later, overall mean difference +1.4 +/- 6.2%) and in 14 34 patients (8-11 months later, overall mean difference -1.4 +/- 9.0%). Weight changes correlated with changes in body cell mass (r(2) = .69, p < .001) and in body fat (r(2) = .29, p < 0.05), but not extracellular mass. Underlying conditions such as AIDS definition, fever, and diarrhoea correlated to prior weight loss (p < .001) but not to the outcome of counselling. Low energy intake (before counselling, < 31.5 kcal/kg) did not correlate to prior weight loss but it predicted further weight loss (p < 0.05 towards normal intake). High energy intake (> 38.5 kcal/kg) correlated (p < 0.05) with more prior weight loss but not with further weight changes. Nutritional counselling may be an effective first-line intervention for malnourished HIV infected patients. More than half of patients gain weight without other nutritional treatment. Whereas the severity of malnutrition is influenced by the underlying disease, fever, and diarrhoea, the course of weight change after nutritional intervention is not. Counselling may reduce the nutritional impact of these risk factors. In patients with low spontaneous intake, efficacy of counselling alone is limited, but it may help to identify those who require more invasive nutritional treatment.     

Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism

Formyl peptides activate superoxide anion (O₂ ^–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O₂ ^– formation via H₂-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H₂-receptor agonists in the guinea pig atrium, on O₂ ^– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O₂ ^– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O₂ ^– formation in neutrophils. In HL-60 cells, guanidines per se activated O₂ ^– formation. The stimulatory effects of guanidines on O₂ ^– formation were not inhibited by H₁- or H₂-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and G_i/G_o-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O ₂ ^– formation.     

Left ventricular assist device improves survival in children with left ventricular dysfunction after repair of anomalous origin of the left coronary artery from the pulmonary artery

BACKGROUND: Repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in infants carries a high operative risk, particularly in infants with myocardial infarction and poor left ventricular function. The marked recovery of left ventricular function reported late after repair, however, suggests that an aggressive approach to repair should be undertaken. METHODS: Of 31 children undergoing primary repair of ALCAPA at our institution from 1987 to 1996, 26 were infants (6 weeks to 9 months old). All but 2 had severe left ventricular dysfunction, and 8 had moderate to severe mitral regurgitation. Seven children were unable to be weaned from cardiopulmonary bypass because of poor left ventricular function and elevated left atrial pressure. These 7 children were placed on mechanical left ventricular support using a centrifugal pump, with support ranging from 2.2 to 70.6 hours. RESULTS: One child died shortly after the start of left ventricular assist (2.2 hours), and another died of arrhythmia within 24 hours after successful decannulation. All 5 survivors had significant improvement in left ventricular function, with 2 requiring late mitral valve repair. CONCLUSIONS: Infants with ALCAPA who have severe left ventricular dysfunction represent a higher risk group for repair. However, with use of mechanical circulatory support in those unable to be weaned from cardiopulmonary bypass, a high survival rate can be achieved with good long-term recovery. We conclude that an aggressive approach to early repair in all children with ALCAPA is warranted, regardless of the degree of left ventricular dysfunction.     

Influence of selective phosphodiesterase inhibitors on human neutrophil functions and levels of cAMP and Cai

Summary Chromatographic analysis of 3,5-cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the cytosol of human neutrophils shows the predominant presence of PDE IV (cAMP specific) and PDE V (cGMP specific). PDE IV is characterized by (1) cAMP selectivity, (2) a K_M for cAMP of 1.2 M and (3) a typical rank order of IC ₅₀-values for PDE inhibitors: 0.13, 0.17, 47 and 9.5 M for PDE IV selective rolipram, PDE III/IV selective zardaverine, PDE III selective motapizone and unselective 3-isobutyl-l-methylxanthine (IBMX), respectively. Functions of polymorphonuclear leukocytes (PMN) such as N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated superoxide release and fMLP/thimerosal elicited leukotriene (LT) biosynthesis are inhibited by these PDE inhibitors with the same rank order and even lower IC₅₀-values. Measurements of changes in cytosolic Ca_i in Fura-2 loaded PMN demonstrate a transient Ca_i increase after stimulation with 0.1 M fMLP and an additional sustained elevation of Ca_i levels in the presence of thimerosal. PDE inhibitors suppress this sustained phase of Ca_i release with the same rank order of IC₅₀-values as LT biosynthesis. The correlation between fMLP/thimerosal-induced LT biosynthesis and Ca_i levels reveal a Ca_i threshold of 150 nM for arachidonic acid metabolism. cAMP levels in PMN were elevated by PDE inhibitors alone by less than 2-fold. In the presence of fMLP however, cAMP was increased up to 10-fold and the efficacy of PDE inhibitors to increase cAMP paralleled their potency to inhibit PDE IV. It is concluded that (1) suppression of PMN functions is achieved by PDE IV inhibition, (2) necessary cAMP elevations are within 50% increase, (3) superoxide release was affected by cAMP/protein kinase A (PKA) directly whereas (4) for inhibition of LT biosynthesis a cAMP related reduction of Ca-influx is involved. Send offprint requests to Ch. Schudt at the above address     

Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10

The cytokine interleukin-10 (IL-10) plays a pivotal regulatory role in tolerizing exogenous antigens. Experimental data indicate that low cellular availability of the vitamin D hormone 1,25-dihydroxyvitamin D [1,25(OH)2D] results in a down-regulation of IL-10 concentrations. The tissue production of an adequate amount of 1,25(OH)2D depends on a high circulating 25-hydroxyvitamin D (25-OHD) level. The present study was thus aimed at evaluating the associations between season of birth, vitamin D status, and the allergy risk markers IL-10 and total immunoglobulin (IgE) in newborns. Cord blood was obtained from 49 infants born during the summer half year (mid-April to mid-October, geographic latitude 51 degrees N) and from 47 infants born during the winter half year (mid-October to mid-April, geographic latitude of 51 degrees N). Serum levels of 25-OHD were 99% higher, and IL-10 levels were 43% higher in the summer half year compared with the winter half year (p < 0.001 and p = 0.018). Moreover, the ratio of IL-10 to total IgE was 124% higher in the summer half year compared with the winter half year (p = 0.039). Serum levels of 25-OHD were correlated with IL-10 levels (r = +0.22; p < 0.05). Mothers' age, gestational ages, birth weights and serum 1,25(OH)2D levels did not differ between study groups. We conclude that the low vitamin D status of infants born in winter may at least in part adversely affect biomarkers of allergy risk.     

Chinikomycins A and B: isolation, structure elucidation, and biological activity of novel antibiotics from a marine Streptomyces sp. isolate M045

In our screening of marine Streptomycetes for bioactive principles, two novel antitumor antibiotics designated as chinikomycins A (2a) and B (2b) were isolated together with manumycin A (1), and their structures were elucidated by a detailed interpretation of their spectra. Chinikomycins A (2a) and B (2b) are chlorine-containing aromatized manumycin derivatives of the type 64-pABA-2 with an unusual para orientation of the side chains. They exhibited antitumor activity against different human cancer cell lines, but were inactive in antiviral, antimicrobial, and phytotoxicity tests.     

Sulfemodin 8-O-beta-D-glucoside,a new sulfated anthraquinone glycoside,and antioxidant phenolic compounds from Rheum emodi

A sulfated emodin glucoside, emodin 8-O-beta-D-glucopyranosyl-6-O-sulfate (1), was isolated from the roots of Rheum emodi in an investigation of the active constituents of this Nepalese medicinal plant, and its structure was determined by spectroscopic and chemical methods. Additionally, two rare auronols, carpusin (2) and maesopsin (3), besides other anthraquinones and phenolics, were isolated and identified. Compounds 2 and 3 showed significant antioxidant activity in the DPPH assay, while chrysophanol, physcion, and emodin and their 8-O-glucosides were found to be inactive.