Differences in chronic spontaneous urticaria between Europe and Central/South America: results of the multi-center real world AWARE study.

BACKGROUND: Global chronic urticaria (CU) disease experience and management is not well documented. This study descriptively compares these aspects among CU patients residing in Europe (EU) and Central and South America (C/SA). METHODS: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global prospective, non-interventional study of CU in the real-world setting. Patients were ≥ 18 years with a diagnosis of H1-antihistamine-refractory CU for > 2 months. Differences between the EU and C/SA regions in demographic and clinical characteristics, quality of life (QoL), work and activity impairment, pharmacological treatment, and healthcare resource use were examined. RESULTS: In total, 4224 patients were included in the analysis (C/SA 492; EU 3732). Rates of untreated patients were greater in the C/SA region (45.1% vs. 31.9%; P < 0.005) and escalation to third-line therapy was rare in both regions. Differences in disease experience emerged, with C/SA patients more commonly experiencing angioedema (C/SA 50.8% vs. EU 46.1%; P = 0.03) or comorbid chronic inducible urticaria (C/SA 30% vs. EU 22%; P < 0.001). Correspondingly, rates of uncontrolled urticaria were higher among C/SA patients (82.8% vs. 77.5%; P = 0.017) and patients in the C/SA region showed significantly greater work and activity impairment (absenteeism: 10.4 ± 19.7 vs. 6.7 ± 19.0, P = 0.004; presenteeism: 30.3 ± 31.9 vs. 24.4 ± 25.8, P = 0.001; work productivity loss: 33.9 ± 33.9 vs. 26.5 ± 27.5, P < 0.001; activity impairment: 37.7 ± 34.7 vs. 32.7 ± 30.1, P = 0.001). However, QoL impairment was greater in the EU region (Dermatology Life Quality Index: C/SA 6.5 ± 5.9 vs. EU 8.3 ± 7.0; P < 0.001). There was a significant difference in use of healthcare resources, including emergency services (39.6% vs. 29.3%; P < 0.001), hospitalization (7.7% vs 21.9%; P < 0.001) general practitioners (31.7% vs 57.3%; P < 0.001), and additional allergists or dermatologists (50.6% vs. 47.3%, P < 0.001), among patients in the C/SA and EU region, respectively. In both regions, patients with a primary diagnosis of CU with angioedema had significantly greater impairment in work and non-work activities and healthcare resource utilization compared to those without angioedema. CONCLUSIONS: This study revealed that CU is a heterogeneous condition with differences in healthcare utilization and outcomes between EU and C/SA. However, overall there is a high unmet need of H1-antihistamine-refractory CU patients, which is associated with high use of healthcare resources, and has a large negative effect on QoL and work productivity.

Antimycobacterial evaluation of germacranolides.

The minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis and M. avium of parthenolide, costunolide, 1 (10)-epoxycostunolide and other germacranolide-type sesquiterpene lactones and derivatives were determined by use of a radiorespirometric bioassay. Structure-activity relationship studies with natural and semisynthetic sesquiterpene lactones suggested that the alpha-methylene-gamma-lactone moiety is an essential, but not sufficient, structural requirement for significant in vitro activity against M. tuberculosis and M. avium.

Alkyl glycerol monoethers in the marine sponge Desmapsamma anchorata.

1-O-Hexadecylglycerol (chimyl alcohol), 1-O-heptadecylglycerol and 1-O-octadecylglycerol (batyl alcohol) have been identified as the major native constituents of a mixture of free alkyl glycerol ethers isolated from the contained water and the methanolic extract of the sponge Desmapsamma anchorata. Minor components were the free C14, C15, C19, C20 and C21 alkyl glycerol monoethers. The alkyl glycerol monoethers were analyzed and identified by gas chromatography/mass spectrometry of their isopropylidene derivatives. This is the first report on the occurrence of free C15, C19, C20 and C21 alkyl glycerol monoethers in a sponge.

Factors predicting re-referral following crisis intervention for community-based persons with developmental disabilities and behavioral and psychiatric disorders.

Characteristics of 98 clients re-referred to receive services from a community-based crisis intervention program were compared to those of program clients who were served during the same 5.25-year period who were not referred. The majority of re-referrals occurred because of the same challenging behavior causing initial referral. Eight-eight percent of re-referral clients received the additional referral by 2 years after initial discharge. For persons under 30, nonfamily residence and initial diagnosis of self-injurious behavior were the strongest predictors. For those over 30, the most important factor was aggression. Recidivism following crisis intervention appears to be a complex function of client characteristics and community capabilities.

Characteristics of children and adolescents with mental retardation and frequent outwardly directed aggressive behavior.

Two interrelated cross-sectional studies were conducted to expand earlier findings about correlates of outwardly directed aggressive behavior in children with mental retardation. In Study 1 we compared children with mental retardation, 27 with and 23 without aggression. Aggression was best predicted by concurrent self-injurious behavior (SIB). In Study 2 we examined the likelihood that aggression was predicted by concurrent SIB and other nondestructive maladaptive behaviors in an archival cohort of 701 children younger than 21 with IQs below 70. Self-injurious behavior significantly predicted outwardly directed aggression for all children regardless of age. Additional predictors besides SIB showed only minimal improvements in model R2 values. Results were discussed in light of recent research proposing a common basis for aggression and SIB.

Characteristics of community-based individuals with mental retardation and aggressive behavioral disorders.

A cohort of 199 individuals with mental retardation referred for behavioral and psychiatric crisis intervention services was studied to determine attributes differentiating physically aggressive behavior from other behavioral problems. Individuals with aggressive and nonaggressive behavior had similar neurological histories and current medical status and similar levels of seizure disorders and CNS abnormalities. Aggressive individuals more often had psychiatric diagnoses of organic brain syndrome, but frequencies of this diagnosis in each group were small. Current aggression was predicted by gender, level of mental retardation, and history of previous institutional placement; the strongest predictor was history of aggression. These data suggest a complex equation to describe social inadequacy involving interactions between CNS functioning and developmental cognitive and social variables that are only partially defined at this time. Further work to characterize this interaction almost certainly must include a prospective longitudinal analysis of social and developmental functions early in life.

Preliminary results on the protective effect of (-)-edunol, a pterocarpan from Brongniartia podalyrioides (Leguminosae), against Bothrops atrox venom in mice.

(-)-Edunol a prenylated pterocarpan was isolated from the roots of two Mexican 'snakeweeds', Brongniartia podalyrioides and B. intermedia (Leguminosae). Edunol (3.1 mg/kg, i.p.) reduced the expected mortality of mice previously treated by the same route with the LD50 of the venom of the serpent Bothrops atrox. The molecular structure and properties of edunol are similar to those previously reported for cabenegrins A-I and A-II.

Zoapatle. XII. In vitro effect of kaurenoic acid isolated from Montanoa frutescens and two derivatives upon human spermatozoa.

Zoapatle aqueous crude extract (ZACE) from Montanoa tomentosa has been used as an oral contraceptive in traditional Mexican medicine for centuries. Kaurenoic acid, as isolated from Montanoa frutescens, and the methyl esters of 15-hydroxy-dihydro-kaurenoic acid and 15-keto-dihydro-kaurenoic acid were tested in vitro on human sperm motility and viability. The estimated ED50 concentrations immobilization were 374, 126 and 58 micrograms/ml, respectively using 15 X 10(6) sperms/500 microliter. Kaurenoic acid and both of its derivatives displayed only weak to negligible capacity for killing human sperms.

PIP: The effects on human sperm motility and viability of 3 compounds isolated from an aqueous extract of Montanoa frutescens Cerv (Compositae, Heliantheae) were tested. The plant is related to the zoapatle, traditionally used as a contraceptive, and known to have uterotonic and luteolytic activity. Kaurenoic acid, its 15 hydroxy- and its methyl ester were prepared from the polar fraction, and dissolved in 95% ethanol at a concentration of 10 mg/ml. Human sperm, suspended in Bigger's Whitten and Wittingham medium at a final concentration of 15 million sperm per 500 mcl were incubated at 37 degrees C. for 60 seconds. Judging sperm motility under phase contrast microscopy, kaurenoic acid was 0.89 times less effective, and the hydroxy kaurenoic acid 2.6 times more effective than verapamil, while the keto derivative was 5.7 times more potent than verapamil at the same concentration. Sperm viability assessed by vital staining was hampered only about 10% by the keto-kaurenoic acid, 21% by kaurenoic acid, and 33% by hydroxy-kaurenoic acid. Doses required for immobilization of 50% of human sperms ranged from 58 to 374 mcg/ml. This is 225 times lower than that reported for gossypol in vitro, and much lower than the millimolar range needed to inactivate sperm with nonoxynol. Thus these drugs may prompt a search for analogs useful in vaginal contraceptives.

Cassine, an antimicrobial alkaloid from Senna racemosa.

The leaves of Senna racemosa yielded the piperidine alkaloid cassine and an inositol methyl ether. Antimicrobial screening of the compounds revealed antibacterial activity of cassine with minimum inhibitory concentrations of 2.5 mg/ml for Staphylococcus aureus and Bacillus subtilis and 5.0 mg/ml for Candida albicans.

Encelin: a fungal growth inhibitor.

A known sesquiterpene lactone, encelin, isolated from the Mexican species Montanoa speciosa (Compositae), was assayed for biocidal activity on fungal cells of Mucor rouxii. The results indicate that encelin has a determining action on growth and the morphogenetic process of fungal cells.

Triterpenoids from Tillandsia fasciculata.

The leaves of Tillandsia fasciculata afforded four tetracyclic triterpenoids of the cycloartane type, two new compounds identified as cyclolaudenyl formate (2) and the (24S)-24-isopropenyl cycloartanone, which we named tillandsinone (1), and the known cyclolaudenone (3) and cyclolaudenol (4).

[Alternative solutions for postoperative pain in teeth with necrotic pulp]. / Alternativas de solución para el dolor posoperatorio en dientes con pulpa necrótica.

Both the literature and clinical experience have verified that necrotic root canals, with or without periapical lesion, display a confusing response to the various tests for pulp vitality. As suggested by clinical and histopathological research studies, these lesions are due to a defense reaction from the periapical connective tissue, in response to bacterial infections which alter host tissues. Diminishing the frequency of postoperative pain in endodontic treatment is currently a leading concern, and this study aimed to evaluate the different variables involved in root canal therapy, so as to recommend the most suitable approach, without losing sight of the main goal at hand: a successful endodontic treatment. The present study was performed on 200 necrotic root canals, using frontal teeth, upper and lower premolars and molars, both with straight or curved canals. Avoiding damage to the periapical regions, the study concluded, is of prime importance in lowering the frequency of postoperatory pain. Also, the presence of periapical pain is vitally important in the appearance of postoperatory pain, and it is in such cases that cleansing must be adopted as a routine clinical procedure.

Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia subtomentosa.

In a bioassay guided search for antimycobacterial compounds from higher plants, the root extracts of Elecampane (Inula helenium L.; Asteraceae) and Sweet Coneflower (Rudbeckia subtomentosa Pursh.; Asteraceae) were chemically investigated for their active constituents. Chromatographic fractions of root extracts of l. helenium, which exhibited significant activity against Mycobacterium tuberculosis, provided the known eudesmanolides alantolactone, isoalantolactone, and 11 alpha H, 13-dihydroisoalantolactone. Peracid epoxidation of alantolactone and isoalantolactone provided 5 alpha-epoxyalantolactone and 4(15) alpha-epoxyisoalantolactone, respectively and oxidation of alantolactone with OsO4 gave 11,13-dihydroxyalantolactone. Active fractions from R subtomentosa contained the known alloalantolactone and 3-oxoalloalantolactone. The structures of the above compounds were established by spectroscopic methods including 1D and 2D NMR techniques as well as spectral comparison with previously reported data. The molecular structure of 5 alpha-epoxyalantolactone was determined by single crystal X-ray diffraction. Eleven natural and semisynthetic eudesmanolides were tested in a radiorespirometric bioassay for activity against M. tuberculosis. 5 alpha-Epoxyalantolactone and encelin from Montanoa speciosa showed minimum inhibitory concentrations (MICs) of 8 and 16 micrograms ml-1, respectively. Alantolactone, isoalantolactone and its 4 alpha, 15-epoxide, 1,2-dehydro-3-epi-isotelekin and alloalantolactone gave MICs of 32 micrograms ml-1. All other compounds showed MIC values of 128 micrograms ml-1 or higher.

Crisis intervention for community-based individuals with developmental disabilities and behavioral and psychiatric disorders.

When individuals with a developmental disability experience a behavioral or psychiatric crisis, their community placement may be threatened. A model crisis intervention program for individuals with dual diagnoses was discussed and performance and outcomes of such a service for 267 children and adults reviewed. Analysis indicated that 69% of the individuals required only one crisis intervention. Of the 31% requiring two or more, nearly all were re-referred earlier than 2 years post initial crisis intervention. The central, gulf-bridging role of a crisis intervention service in a comprehensive, coordinated, community-based mental health system for dually diagnosed individuals was discussed.

Characteristics of older adults with intellectual disabilities referred for crisis intervention.

The aim of the present study was to identify the age correlates of behavioural crises in adults with intellectual disability (ID) living in the community. The cohort consisted of 185 clients (IQ < 70), ranging in age from 20 to > 70 years, who were referred to a crisis intervention programme specializing in services to individuals with dual diagnosis over a 7-year period. A retrospective cross-sectional analysis of historical and contemporaneous variables was completed. Referrals for crisis intervention were not related to the age of the client Aggression and non-compliant behaviour occurred with similar frequency in all age groups. Other behaviours, including withdrawal, self-injury, stereotypy and symptoms of psychiatric disorders, occurred less often in older clients. Severity of ID affected the pattern of behavioural crises that resulted in referral. The results suggest that people with ID residing in community settings still experience behavioural crises as they grow older. Confirmation of the trends reported in the present study might signal a need for accelerating the development of comprehensive age-span community mental health and behavioural supports.

Clinical cross-reactivity between amoxicillin and cephadroxil in patients allergic to amoxicillin and with good tolerance of penicillin.

In recent years, patients allergic to amoxicillin (AX) but with good tolerance of penicillin G (PG) have been described. It has been suggested that the epitope implicated in this type of sensitization might be located on the side-chain of the AX molecule. Thus, cross-reactivity between AX and cephadroxil (CEPH), a cephalosporin which shares an identical side-chain with AX, is suspected. This study aimed to demonstrate clinical cross-reactivity between AX and CEPH in patients allergic to AX and showing good tolerance of PG. In 76 of 576 subjects with suspected allergic reaction to PG and/or AX, the diagnosis of allergy was confirmed. All of these had specific IgE to PG, penicillin V, or AX, and/or positive skin tests to PPL (penicilloyl-polylysine), or MDM (minor determinant mixture), or PG, or AX, and/or positive challenge tests with PG and/or AX. Sixteen subjects (21%) allergic to AX (11 with positive skin test and five with positive challenge test to AX) and good tolerance of PG (all with negative parenteral challenge test) were selected. These 16 patients were subsequently challenged with CEPH (up to 500 mg). Fourteen patients tolerated CEPH, and two (12%) had an immediate allergic reaction. Our study indicates that allergy to the side-chain of aminopenicillins seems to have little clinical relevance in patients with allergic reactions to aminopenicillins but with good tolerance of PG, as 88% of patients with this clinical characteristic tolerate a cephalosporin which shares an identical side-chain. It seems that IgE from most of these patients recognizes an epitope different from the side-chain and the beta-lactam ring.