Changing threshold for cataract surgery in Denmark between 1980 and 1992. Results from the Danish Cataract Surgery Outcomes Study. II

In Denmark the number of cataract extractions has increased 350% from 1980 to 1991. During the same period the elderly population at risk has only increased 17%, and thus cannot account for the large increase in the number of extractions. In order to investigate whether more comprehensive clinical indications could be a possible explanation, we compared pre-operative visual acuity and visual impairment in two consecutive samples of Danish cataract surgery patients obtained in 1980 (n = 73) and in 1992 (n = 290). Criteria for inclusion were similar and both samples were representative for the whole country. During the period mean pre-operative visual acuity increased from 0.04 to 0.16 in the eye enlisted for surgery (p < 0.00001). Visual functional impairment could be compared by using the same questionnaire for patient interview in 1992 as was used in 1980. In 1992 the degree of impairment was significantly less for reading, outdoor orientation and self care activities. A change in surgical threshold or clinical indications for surgery appears to be a major contributing factor to the large increase in surgical rates, even though a trend to perform second eye cataract surgery more often might also be of some importance.     

Cicaprost and the type IV phosphodiesterase inhibitor, rolipram, synergize in suppression of tumor necrosis factor-alpha synthesis

Suppression of tumor necrosis factor-alpha (TNF) synthesis is one major target in pharmacological immunomodulation. We now showed the synergistic suppressive effect of the specific type IV phosphodiesterase inhibitor, rolipram, and of the stable prostacyclin analogue, cicaprost, on TNF synthesis. This effect was seen with lipopolysaccharide and Staphylococcus epidermidis as stimuli in human peripheral blood mononuclear cells and in whole blood. Lipopolysaccharide-induced TNF synthesis by mononuclear cells decreased from 3.4 ng/ml to 1.5 ng/ml in the presence of 100 nM rolipram and to 0.7 ng/ml in the presence of 10 nM cicaprost. The combination of both agents suppressed TNF synthesis more than 10-fold, to 0.3 ng/ml. Synergistic suppression was also demonstrated for TNF mRNA.     

Characterizing patterns of drug-taking behavior with a multiple drug regimen in an AIDS clinical trial

OBJECTIVE: To characterize drug-taking behavior using continuous electronic monitoring in an AIDS clinical trial. SETTING: This was a substudy of AIDS Clinical Trials Group (ACTG) protocol 175, a phase II/III study of dideoxynucleoside monotherapy versus combination therapy in asymptomatic HIV-positive subjects. Participants were required to comply with regimens containing zidovudine, zalcitabine and didanosine, or matching placebos; the total daily pill count was 16. DESIGN: For participants at two ACTG 175 sites, electronic devices were used to monitor drug-taking behavior of all study medications over a period of approximately 90 days. MEASUREMENTS: Four indices of drug-taking behavior were calculated and their distributions and relationship to the prescribed regimen were examined. RESULTS: Data from 41 subjects were analyzed. Of the prescribed doses of zidovudine, zalcitabine and didanosine, 88, 84 and 82%, respectively, were taken. Of these, 55, 66 and 79%, respectively, were taken at the prescribed dosing frequency. The median percentage of days on which participants failed to take any of the doses was 2-5%. There was a trend towards lower adherence in the combination therapy arms compared with those assigned to receive monotherapy. In this analysis, older patients demonstrated better adherence, although patient characteristics, in general, were poorly predictive of adherence. CONCLUSION: Drug-taking behavior for all three active study medications differed from that prescribed. One result of this erratic adherence was that study participants sustained little antiretroviral effect during more than 25% of the monitoring period.     

West Nile encephalitis epidemic in southeastern Romania

BACKGROUND: West Nile fever (WNF) is a mosquito-borne flavivirus infection endemic in Africa and Asia. In 1996, the first major WNF epidemic in Europe occurred in Romania, with a high rate of neurological infections. We investigated the epidemic to characterise transmission patterns in this novel setting and to determine its origin. METHODS: Hospital-based surveillance identified patients admitted with acute aseptic meningitis and encephalitis in 40 Romanian districts, including Bucharest. Infection was confirmed with IgM capture and indirect IgG ELISAs. In October, 1996, we surveyed outpatients in Bucharest and seven other districts to estimate seroprevalence and to detect infected patients not admitted to hospital. We also measured the rates of infection and seropositivity in mosquitoes and birds, respectively. RESULTS: Between July 15 and Oct 12, we identified 393 patients with serologically confirmed or probable WNF infection, of whom 352 had acute central-nervous-system infections. 17 patients older than 50 years died. Fatality/case ratio and disease incidence increased with age. The outbreak was confined to 14 districts in the lower Danube valley and Bucharest (attack rate 12.4/100000 people) with a seroprevalence of 4.1%. The number of mild cases could not be estimated. WN virus was recovered from Culex pipiens mosquitoes, the most likely vector, and antibodies to WN virus were found in 41% of domestic fowl. INTERPRETATION: The epidemic in Bucharest reflected increased regional WNF transmission in 1996. Epidemics of Cx pipiens-borne WNF could occur in other European cities with conditions conducive to transmission.     

Antithrombotic effect of crotalin, a platelet membrane glycoprotein Ib antagonist from venom of Crotalus atrox

A potent platelet glycoprotein Ib (GPIb) antagonist, crotalin, with a molecular weight of 30 kD was purified from the snake venom of Crotalus atrox. Crotalin specifically and dose dependently inhibited aggregation of human washed platelets induced by ristocetin with IC50 of 2.4 microg/mL (83 nmol/L). It was also active in inhibiting ristocetin-induced platelet aggregation of platelet-rich plasma (IC50, 6.3 microg/mL). 125I-crotalin bound to human platelets in a saturable and dose-dependent manner with a kd value of 3.2 +/- 0.1 x 10(-7) mol/L, and its binding site was estimated to be 58,632 +/- 3, 152 per platelet. Its binding was specifically inhibited by a monoclonal antibody, AP1 raised against platelet GPIb. Crotalin significantly prolonged the latent period in triggering platelet aggregation caused by low concentration of thrombin (0.03 U/mL), and inhibited thromboxane B2 formation of platelets stimulated either by ristocetin plus von Willebrand factor (vWF), or by thrombin (0.03 U/mL). When crotalin was intravenously (IV) administered to mice at 100 to 300 microg/kg, a dose-dependent prolongation on tail bleeding time was observed. The duration of crotalin in prolonging tail bleeding time lasted for 4 hours as crotalin was given at 300 microg/kg. In addition, its in vivo antithrombotic activity was evidenced by prolonging the latent period in inducing platelet-rich thrombus formation by irradiating the mesenteric venules of the fluorescein sodium-treated mice. When administered IV at 100 to 300 microg/kg, crotalin dose dependently prolonged the time lapse in inducing platelet-rich thrombus formation. In conclusion, crotalin specifically inhibited vWF-induced platelet agglutination in the presence of ristocetin because crotalin selectively bound to platelet surface receptor-glycoprotein Ib, resulting in the blockade of the interaction of vWF with platelet membrane GPIb. In addition, crotalin is a potent antithrombotic agent because it pronouncedly blocked platelet plug formation in vivo.     

The role of adhesion molecules in human leukocyte attachment to porcine vascular endothelium: implications for xenotransplantation

Many obstacles still prevent successful xenotransplantation of porcine donor organs. When hyperacute rejection is averted, transplanted pig organs are subject to acute vascular and cellular rejection. In autologous systems, leukocyte recruitment into inflamed tissues involves selectins, integrins, and Ig family members. To determine whether these mechanisms allow human leukocytes to effectively enter porcine grafts, the pathways by which human leukocytes adhere to TNF-alpha-stimulated porcine aortic endothelium were examined under static and physiologic flow conditions. L-selectin and E-selectin had overlapping functions in neutrophil capture and rolling, whereas Ab blockade of E-selectin and the beta2 integrins inhibited firm arrest of rolling neutrophils. Combined blockade of selectins and beta2 integrins resulted in negligible human neutrophil attachment to pig endothelium. Lymphocyte attachment to porcine endothelium was primarily L-selectin mediated, whereas beta2 integrin and VCAM-1/very late Ag-4 (VLA-4) interactions promoted static adhesion. Concurrent beta2 integrin, VLA-4, VCAM-1, and L-selectin blockade completely inhibited lymphocyte attachment. Thus, interactions between leukocyte-endothelial cell adhesion receptor pairs remained remarkably intact across the human-porcine species barrier. Moreover, disrupting the adhesion cascade may impair the ability of human leukocytes to infiltrate a transplanted porcine organ during rejection.