Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction.

Recent clinical studies comparing accelerated versus bolus administration of alteplase tissue plasminogen activator (t-PA) suggest similar thrombolytic efficacy, but reveal higher bleeding complications among older patients during the double-bolus regimen. The objective of the present study was to characterize the hemostatic profile of t-PA administered as double-bolus doses of 50 mg, at intervals of 30 minutes. Among 50 patients with acute myocardial infarction treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis parameters, as well as t-PA levels, were monitored. Monitored t-PA levels peaked at 5 and 35 minutes and were detectable within the therapeutic range even after 90 minutes. Marked systemic fibrinolytic activation was indicated by 75% depletion of both plasminogen and fibrinogen, as well as by 19-fold and 300-fold increases of fibrin degradation and fibrinogen degradation products. Plasminogen-activator inhibitor activity was completely suppressed. Pronounced procoagulant activation was reflected by a 3.4-fold increase of both factor XIIa and prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin complex. Independent of t-PA weight dosage, fibrinolytic activation was more pronounced among older patients (> or = 63 years). We conclude that t-PA after bolus administration has a long half-life. Double-bolus regimen leads to a long-lasting systemic fibrinolytic state, which is even more remarkable among older patients--a fact that may explain the higher bleeding complications reported for this age group.

Combined dipyridamole and dobutamine echocardiography in myocardial hibernation: comparison with thallium uptake in patients after percutaneous transluminal coronary revascularization under circulatory support.

OBJECTIVE: To investigate the specificity and sensitivity of the combination of dipyridamole and dobutamine echocardiography for predicting functional recovery in patients with reduced ventricular function after coronary angioplasty. METHODS: Twenty-five patients, mean (SD) age 60.8 (10) years, with previous myocardial infarction (> 3 months), angiographically assessed coronary artery disease, and resting regional dysfunction (left ventricular ejection fraction < 35%) were studied. They underwent rest-redistribution thallium Tl-201 single photon emission computed tomography, and low-dose pharmacologic stress echocardiography with dobutamine (up to 10 microg/kg per minute), ultra low-dose dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine administration. RESULTS: The rate of agreement between Tl-201 and stress echo was 59% for dipyridamole, 62% for dobutamine, and 71% for combined dipyridamole-dobutamine (P <.05 vs dipyridamole and vs dobutamine). Combined dipyridamole-dobutamine showed a higher sensitivity (89%) than Tl-201, dobutamine, or dipyridamole (84%, 78%, and 80%). Specificity was lower for functional recovery prediction with Tl-201 (60%) compared with dobutamine (89%), dipyridamole (90%), and combined dipyridamole-dobutamine (91%). CONCLUSION: Thallium is more sensitive than dipyridamole or dobutamine; the sensitivity gap is filled with combined dipyridamole-dobutamine. Pharmacologic stress echocardiography is more specific than Tl-201 scintigraphy.

[Incidence and distribution pattern of pulmonary saddle emboli: Diagnosis by electron beam tomography (EBT)]. / Häufigkeit und Verteilungsmuster pulmonalerSattelembolien: Diagnostik mittels Elektronenstrahl-Computertomographie (EBT).

PURPOSE: To determine the incidence of acute pulmonary emboli extending across the bifurcation of the main pulmonary artery, lobar arteries or segmental arteries (interpulmonary, interlobar or intersegmental saddle emboli, respectively). METHODS: 128 patients with clinically suspected acute pulmonary embolism underwent electron beam tomography (EBT). 140 scans were acquired in the continuous volume scanning mode (3 mm slice thickness). 100 ml of contrast material were intravenously administered. Studies were reviewed for the presence of acute pulmonary embolism and the number and location of interpulmonary, interlobar or intersegmental saddle emboli. Saddle emboli were defined as emboli extending across the bifurcation of a vessel into both branches by at least 5 mm each. RESULTS: 30 of 128 (23.4 %) patients (15 men; mean age 59 +/- 17 years) had acute pulmonary embolism. One or more saddle emboli were present in 20 of 30 patients (66.7 %), a total of 77 saddle emboli were detected ranging from 1 to 10 per patient. Distribution of the saddle emboli in the 20 patients was as follows: 5 interpulmonary, 28 interlobar and 44 intersegmental. CONCLUSIONS: Pulmonary saddle emboli are present in the majority of patients with acute pulmonary embolism. They are often multiple and may be found at different levels of the pulmonary arterial vasculature.

Specific Contributions of Politics, Economics, and Toxicology in Setting Socially Consensual Limit Values

/ Limit values are legal limits for the concentrations of substances in the environment. They must be agreed upon in a consensual procedure between science, economics/technology, and political forces. This is a crucial political precondition for their social acceptance. The arguments put forward to justify their expediency and numerical level are based not only on risk-benefit considerations but also on the aspect of the technical avoidability of direct and indirect exposure. The critical assessment of the direct benefit of specified exposures falls within the responsibility of economics/technology, whereas criteria for their potential adverse effects (direct and indirect) are provided by medicine/biochemistry and/or ecology. Within this concept, the avoidance of nonbeneficial-even if not openly adverse-exposure is the essential aim of environmental hygiene and should be promoted by politics/science. In general, society or segments thereof reject adverse, accept beneficial, and tolerate unavoidable exposure. Conflicts of interest arise when different groups of society simultaneously define a given exposure as being adverse, beneficial, and unavoidable. Therefore, from the viewpoint of society as a whole, an optimal exposure lies as far as reasonably achievable at a level lower than known or plausible adverse effect thresholds (as defined by toxicology or ecology). This optimal level of exposure must be determined using a transparent and, hence, public procedure.KEY WORDS: Legal limit values; Benefit threshold; Social acceptance; Social tolerability; Adverse effect threshold; Avoidable exposure; Tolerance threshold; Environmental hygiene

[On the action of various factors on the liberation from suppositories (author's transl)]. / Zum Einfluss verschiedener Faktoren auf die Liberation aus Suppositorien.

The authors deal with the effects of five suppository bases on the liberation of aminophenazone, codeine phosphate, phenobarbital natrium and trapidil from suppositories, with regard to the physical properties (melting time, melting range, melting point, viscosity) and the chemical properties (acid number, hydroxyl value, composition of the bases) of the bases and the suppositories as well as of the drugs used (solubility, particle size). The grouping of the causative factors indicated, which must be weighted differently, leads to the characterization of the mechanisms of liberation and to the interpretation of the considerable differences in liberation.

[On the effect of storage on the release of trapidil from suppositories (author's transl)]. / Zum Einfluss der Lagerung auf die Liberation von Trapidil aus Suppositorien.

It is reported of the effect of storage at different temperatures on the release of Trapidil from Rosupol U suppositories, and of the melting characteristics (melting range, melting time, DTA data). The observed reductions of release are but incompletely reflected by the physical parameters.

[Characterization of storage-induced release reductions in suppositories (author's transl)]. / Charakterisierung von lagerungsbedingten Liberationsminderungen bei Suppositorien.

It is reported of the effect of storage at different temperatures on the release of aminophenazone, codeine phosphate, phenobarbital sodium and trapidil from suppositories, and of the physical parameter of the latter. Depending on the state of division of the drugs in the preparations and on the conditions of storage, drug release from suppositories was more or less affected, which alterations were but incompletely reflected in the physical parameters of the suppositories.

[The bioavailability of trapidil from suppositories (author's transl)]. / Bioverfügbarkeit von Trapidil aus Suppositorien.

In a study with five healthy persons designed to compare the bioavailability of Trapidil from Rosupol U suppositories with that from Witepsol H 15 suppositories, the availability of Trapidil from the Rosupol U suppositories was inferior in four of the five test subjects. The difference in the amounts of released drug observed in vivo was smaller than that found in vitro.

Safe water supply without disinfection in a large city case study: Berlin.

Berlin's water supplies originate exclusively from groundwater. For sustainable water management, river water is treated by flocculation and filtration and used either for artificial groundwater recharge (rivers Spree and Havel) or for bank filtration (Nordgraben and Lake Tegel). Drinking water chlorination was abandoned in Berlin (West) in 1978, and in Berlin (East) in 1992, following German unification. Chlorine consumption for the purpose of weekly performance checks in the chlorination plants of Berlin's 11 waterworks and occasional chlorination within the pipe system following pipe burst events amounts to 2500 kg per year. Based on the annual water demand of 250 million cubic metres, this is equivalent to 0.01 mg of chlorine per litre. Microbiological monitoring at the 11 waterworks and at 383 sampling points within the pipe system shows CFU at less than 10/1 ml-1 and coliforms and E. coli invariably at 0/100 ml-1. In view of the low AOX content, a multiplication of bacteria within the pipe system can be expected to occur not at all or only to a small extent. Resource protection measures, filter backwashing and pipe system maintenance in observance of the relevant technical rules will continue to ensure that the quality of Berlin's drinking water meets stringent hygiene requirements without chlorination.

[Growth of non-sporing anaerobes in an oxygen-free blood culture system (author's transl)]. / Wachstum sporenloser Anaerobier in sauerstoffreiem Blutkulturmedium

The efficacy of the commercially available Vacutainer blood culture system to support the growth of non-sporing anaerobes was compared with two laboratory-prepared blood culture media (supplemented thioglycollate medium and brain heart infusion). The media were inoculated with 10, 100 and 1000 organisms of the species tested, and the number of colony-forming units was determined at intervals of 8-10 hrs. Analogous experiments were performed with batches of the media to which 10% vol/vol of human blood had been added. From the results obtained with strains of Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides splanchnicus, Sphaerophorus necrophorus, Peptostreptococcus anaerobius and Propionibacterium acnes it became obvious that growth of non-sporing anaerobes was significantly enhanced in the Vacutainer culture tubes, whereas Enterobacteriaceae and Streptococcus spp. grew equally well in all the media tested.

Problems with platelet counting in thrombocytopenia. A rapid manual method to measure low platelet counts.

Because most automated platelet counters cannot be relied on in thrombocytopenia, clinicians face a problem when decision making is based on platelet counts. Therefore we evaluated a visual platelet counting method from a blood smear with white blood cells (WBCs) as reference (PCW = platelet count based on WBC). Platelet counting for 74 thrombocytopenic (<120 x 10(9)/L) children was performed with PCW and with an automated counter (impedance principle); both methods were compared with evaluation by phase-contrast microscopy as the standard method. The PCW correlated well with the phase-contrast microscopy evaluation (y = -0.38 + 1.01x, r2 = 0.99). For platelet counts <20 x 10(9)/L the maximal deviation was 2 x 10(9)/L. The correlation between automated counts and the standard method was poor. The regression was y = 9.63 + 0.94x, r2 = 0.86. For platelet counts <20 x 10(9)/L the maximal deviation was 37 x 10(9)/L; on average, 7 x 10(9)/L platelets were counted in excess when compared with the standard method. PCW, in contrast to the automated impedance method, discriminated platelets from nonplatelet particles such as debris, fragments of red blood cells (hemolytic-uremic syndrome [HUS]) and of blast cells, and identified platelets of abnormal size. In addition, the appearance ofplatelets, WBCs, and RBCs gave clues to the etiology of thrombocytopenia, such as leukemia, infection, HUS, familial macrothrombocytopenia, and immune thrombocytopenia. PCW is a fast, reliable platelet counting method requiring less experience than the phase-contrast method. Visual evaluation from a stained smear clearly differentiates platelets and nonplatelet particles in contrast to most automated counters. In addition, the original smear can be preserved and reevaluated.

[Inactivation of bacteria and coliphages in surface water highly polluted by secondary effluent and purified by flocculation and filtration by means of UV irradiation at a pilot plant scale]. / Inaktivierung von Bakterien und Coliphagen in abwasserbelastetem und durch Flockungsfiltration aufbereitetem Oberflächenwasser mittels UV-Bestrahlung in einer halbtechnischen Anlage.

The water of a channel in Berlin which is highly polluted by municipal sewage effluent is treated at the phosphate elimination plant (PEP) Tegel by flocculation and filtration in order to reduce eutrophication in the following Lake Tegel. The elimination of bacteria and coliphages in the effluent of the PEP was investigated in a scale pilot UV irradiation reactor installed at the outlet of the PEP Tegel. The influence of technical parameters such as flow rate and the arrangement of 23 UV lamps in the reactor on the inactivation was tested. The UV irradiation dose was calculated 119 mJ/cm2 and 49 mJ/cm2 at a flow rate of 50 m3/h and 120 m3/h, respectively and for an irradiation zone of 97.5 cm. The colony count of bacteria and concentrations of coliform organisms, E. coli, and feacal streptococci as well as the plaque forming units of coliphages in the influent of the UV reactor were reduced 2-3 lg units by an irradiation dose of 119 mJ/cm2. These elimination was found being only one lg unit at a UV irradiation dose of 49 mJ/cm2. The concentration of E. faecalis and Coliphages f2 seeded into the influent of the UV reactor decreased after UV irradiation by 119 mJ/cm2 by 2-4 lg units and 1-2 power of magnitude, respectively. A UV dose of 49 mJ/cm2 caused only a 90% elimination of E. faecalis and a 75% inactivation of Coliphages f2. Due to heterogenous distribution and the different retention period of the inflowing water in the irradiation zone, the inactivation of E. faecalis and Coliphages f2 was unequal. Both test organisms decreased in the middle of the reactor up to 2 lg units more than at the sides of the reactor. The hygienic-microbiological quality of a secondary effluent from sewage treatment plants can be improved by a combination of flocculation-filtration and UV irradiation due to their additive elimination effect. However, this UV reactor, which was tested under field conditions can only ensure the inactivation of bacteria and coliphages in the pretreated effluent, if more homogenous distribution of the inflowing water can be achieved. Further, the water must be irradiated by a higher UV dose.

Re-opened foramen ovale--a rare cause of postoperative dyspnea following pneumonectomy.

Dyspnea and hypoxemia are common postoperative problems following pneumonectomy. Platypnea, the increased dyspnea in the erect position relieved by assuming a prone position, has been reported as a result of right to left inter-atrial shunt. We report here on our experience with a patient who had severe platypnea with remarkable positional arterial desaturation following right pneumonectomy. After establishing the diagnosis with contrast-enhanced transesophageal echocardiography of the preoperatively undetected interatrial right-left shunt, cardiac surgery led to clinical improvement and resumption of platypnea. Given the rarity of the diagnosis, we think interatrial shunt, based on an open foramen ovale, should be taken into consideration when platypnea occurs in patients as a postoperative complication following lung surgery. Transesophageal echocardiography may be helpful in detecting patients with "anatomical closed but functional open" foramen ovale or genuine inter-atrial septal defect prior to lung surgery.

The elusive structures of pentakis[(triphenylphosphine)gold]ammonium(2+) bi.

[Pentakis[(triphenylphosphine)gold(I)]ammonium(2+)] bis[(tetrafluoroborate)(1-)] was prepared from [tetrakis[(triphenylphosphine)gold(I)]-ammonium(1+)] [tetrafluoroborate(1-)] and [(triphenylphosphine)gold(I)] tetrafluoroborate in hexamethyl phosphoric triamide and tetrahydrofuran at 20 degrees C in 53% yield and crystallized from dichloromethane as the new solvate [[(Ph3P)Au]5N]3 [BF4]6 [CH2Cl2]4. The crystal structure of this product has been determined by single-crystal X-ray methods [monoclinic, P2(1/n), a = 34.200(3), b = 15.285(1), c = 53.127(3) A, beta = 107.262(2) degrees, V = 26521(3) A3, Z = 12, at 153 K]. The lattice contains three independent trinuclear dications that have no crystallographically imposed symmetry and are mutually similar in their molecular structure. The geometry of the [Au5N] core with pentacoordinate nitrogen atoms is intermediate between trigonal-bipyramidal and square pyramidal with severe distortions to minimize the Au-Au distances along some of the edges of the polyhedra. The three structures are thus different from that found previously in the tetrahydrofuran solvate [[(Ph3P)-Au]5N](BF4)2(C4H8O)2, where the geometry of the same trinuclear dication is closer to the trigonal-bipyramidal reference model. The new results are discussed in the light of the structures of tetra(gold)ammonium cations in salts of the type [[(Ph3P)Au]4N]+X- and of related tetra-, penta-, and hexacoordinate poly(gold)phosphonium, -arsonium, -sulfonium, and -selenonium cations.

von Willebrand factor-collagen binding activity is increased in newborns and infants.

von Willebrand factor (vWF) antigen (vWF:Ag) and vWF-collagen binding activity (vWF:CBA) were measured in plasma by parallel quantitative ELISAs in normal newborns and infants (n = 71). The medians for vWF:Ag (IU/ml) and vWF:CBA (U/ml), respectively, were 1.46 and 1.91 for 2-7 day-old (n = 43), 1.22 and 1.40 for 2-4 week-old (n = 14), 1.22 and 1.15 for 2-6-month-old (n = 14) infants and 0.98 and 1.08 (n = 36) in normal adults. Elevated levels of vWF:Ag, but particularly vWF:CBA were seen for up to 4 weeks of life reaching adult levels between 2 and 6 months of life. The elevated levels of the vWF parameters indicate that caution should be exercised when interpreting laboratory data and diagnosing von Willebrand disease in newborns and young infants and warrant the use of age-specific reference ranges. The efficient haemostasis observed during early neonatal life may in part be due to the increased ability of vWF to interact with collagen.

Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

[Reduction of bacteria and viruses in purification plant discharges using microfiltration in a model plant]. / Reduzierung von Bakterien und Viren in Klärwerksabläufen durch Mikrofiltration in einer Modellanlage.

Microfiltration through a membrane matrix of a nominal pore size of 0.2 microns has been applied for advanced treatment of mechanically and biologically treated wastewater. Elimination of bacteria and coliphages as well as the decrease in some chemical constituents were studied at a flow rate of 80 l/h. Microfiltration resulted in a reduction of E. coli, coliform bacteria, fecal streptococci and of coliphages by more than 4 logs in the filtrate. Thus, the quality requirements of EC Directives for bathing water (EC, 76/160) could be maintained. As a result of microfiltration, a 43 +/- 13% removing of the total phosphorous compounds (Pt) in the pre-filtered secondary effluent from 11 +/- 2 mmol/m3 (0.34 +/- 0.06 mg/l) to 6 +/- 2 mmol/m3 (0.19 +/- 0.06 mg/l) was measured. The dosage of FeCl3 (between 30 and 150 mmol/m3) as coagulant before microfiltration improved the reduction of Pt to result in an average value of 75 +/- 16%. After adding FeCl3, orthophosphates (PO4-P) could be efficiently reduced by microfiltration. Thus, PO4-P concentrations in effluent samples were, in most cases, below the detection limit (0.01 mmol/m3).