Establishing local reference intervals for full blood count and white blood cell differential counts in Cape Town, South Africa.

BACKGROUND: Accurate laboratory reference intervals (RIs) are essential to differentiate between health and disease. There are variations in haematological indices within populations relating to gender, age, ethnicity and environment. Iron deficiency is common, has a wide range of clinical morbidities and affects red cell indices. Locally derived RIs for full blood count (FBC) parameters are needed for the Western Cape region of South Africa, after the exclusion of iron deficiency. In addition, information regarding the prevalence of iron deficiency in first-time blood donors would inform blood transfusion services regarding policies to screen for and treat iron deficiency. OBJECTIVES: To establish locally derived RIs for FBC and white blood cell (WBC) differential count parameters in healthy adults in the Cape Town area, by including first-time blood donors and excluding those with iron deficiency and thalassaemic indices. These new locally established RIs could update those in use by the local National Health Laboratory Service. A secondary objective was to establish the prevalence of iron deficiency in first-time blood donors. This would inform blood donation policies regarding screening and appropriate iron supplementation in high-risk groups prior to blood donation. METHODS: This was a prospective, descriptive study with direct convenience sampling. Participants were prospective voluntary blood donors aged between 18 and 60 years, presenting for first-time blood donation. Ethnicity was self-identified. Participants who tested positive for HIV or hepatitis B and/or C viruses were excluded. Prospective participants with iron deficiency, defined by serum ferritin levels below the RI, and those with red cell indices suggestive of an underlying thalassaemia trait were excluded. FBC samples were analysed using a Sysmex XN-1000 cell counter. Statistical non-parametric methods were used to calculate the RIs, according to international guidelines. RESULTS: Of the 774 participants screened, 82 (11%) had iron deficiency and were excluded. Six hundred and sixty-two patients were included for analysis, 409 (62%) female and 253 (38%) male. The majority of the participants, 348 (53%), were between 20 and 29 years of age, with a mean age of 29 years for females and 28 years for males. Participants comprised a mix of the various ethnic groups residing in Western Cape Province. The mean haemoglobin concentration for females was lower than that for males (p<0.0001). There were significant gender differences for total WBC count, absolute neutrophil count and platelet count, with females having higher counts than males. CONCLUSIONS: Locally established, population-specific RIs are essential for the accurate interpretation of haematological indices. This study established locally derived gender-specific RIs for the Cape Town region, after exclusion of iron deficiency. These new RIs have implications for the accurate diagnoses of cytopenias, cytoses and other blood count abnormalities. Iron deficiency is common in first-time blood donors, and screening for iron deficiency using point-of-care testing should be considered.

Role of silver doping on the defects related photoluminescence and antibacterial behaviour of zinc oxide nanoparticles.

The Ag doped ZnO (ZnO:Ag) NPs with a hexagonal wurtzite structure were synthesized by a solution combustion method. X-ray absorption near edge structure (XANES) and X-ray photoelectron spectroscopy (XPS) were used to study the defects, local electronic and atomic structures before and after Ag doping. XPS and XANES studies confirmed the deficiency of concentration of defects in ZnO after Ag doping. The photoluminescence study showed the deep level emission in the orange-red region in addition to the band to band emission. It was also found that the defect related emission of ZnO was decreased with an increasing in Ag concentration. The antibacterial behaviour of ZnO and ZnO:Ag NPs was studied against the gram positive and gram negative bacteria. The role of Ag doping and defects in the ZnO NPs were discussed for the observed antibacterial and photoluminescence behaviour.

Halogenated contaminants in farmed salmon, trout, tilapia, pangasius, and shrimp.

Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzo-p-furans (PCDD/Fs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane diastereomers (HBCDs), and perfluorinated compounds (PFCs) were analyzed in popular farmed fish such as salmon, trout, tilapia, and pangasius and in farmed shrimp. The samples originated from southeast Asia, Europe, and South America. Results show the following: (i) Carnivorous species contained higher contaminant concentrations than omnivorous species. (ii) Contaminant concentrations generally decreased per species in the following order of salmon > trout >> tilapia approximately equal to pangasius approximately equal to shrimp. (iii) Most contaminant concentrations decreased in the following order of PCBs approximately equal to dichloro-diphenyl-trichloroethanes (DDTs) >> hexachlorobenzene approximately equal to pentachlorobenzene approximately equal to dieldrin approximately equal to PBDEs approximately equal to alpha-HBCD approximately equal to perfluorooctane sulfonate (PFOS) >> World Health Organization toxic equivalents (WHO-TEQ) [PCDD/Fs and dioxin-like (dl)-PCBs]. (iv) Contaminant concentrations were very low (mostly <1 ng/g wet weight) and far below the European and Dutch legislative limits. (v) Contaminant concentrations in farmed shrimp, pangasius, and tilapia were lower than those in wild fish, whereas contaminant concentrations in farmed salmon and trout were higher than those in lean wild marine fish. From the five species investigated, salmon is predominantly responsible (97%) for human exposure to the sum of the investigated contaminants. The contribution of trout, tilapia, pangasius, and shrimp is small (3%) because contaminant concentrations and consumption volumes were much lower.

Cortical changes in complex regional pain syndrome (CRPS).

Recent research suggests that changes in cortical structures can contribute to the pathophysiology of Complex Regional Pain Syndrome (CRPS). This review provides an overview of studies showing cortical involvement in CRPS, including mislocalizations of tactile stimuli, changes in size and organization of the somatosensory map, changes in motor cortex representation and body perception disturbances. In addition, we review experimental treatment approaches, such as mirror therapy and motor imagery programs, aimed at restoring the integrity of neural processing in the sensory-motor cortex in individuals with CRPS. The intervention effects are promising and can be theoretically motivated on the basis of established principles of neural organization, although important questions concerning the precise neural mechanisms of action remain unanswered.

Significant improvements in the analysis of perfluorinated compounds in water and fish: results from an interlaboratory method evaluation study.

The 2nd international interlaboratory study (ILS) on perfluorinated compounds (PFCs) in environmental samples was organized to assess the performance of 21 North American and European laboratories on the analysis of PFCs in water and fish. A study protocol was provided to assess accuracy, precision, matrix effects and to study the use of in-house standards. The participants used shared native and mass-labelled standards that were provided for this study to quantify the PFC concentrations in the samples. Matrix effects in the determination of PFCs can be considerable and can decrease the sensitivity, the accuracy and internal standard recoveries. Therefore, two quantification methods were evaluated by all laboratories: standard addition quantification (SAQ) and solvent-based calibration curve quantification (SBCCQ; using mass-labelled internal standards (IS)). The between laboratory reproducibility (i.e. coefficient of variance) was smaller for the SBCCQ results (except for PFBS and PFHxS for which no mass-labelled analogues were available) compared to those obtained by the SAQ method. The within laboratory precision of individual laboratories is good (mean for all PFCs in water 12% and 6.8% in fish). The good performance is partially attributable to the use of well-defined native- and mass-labelled standards. Therefore, the SBCCQ method is recommended. The results show that analytical methods for PFCs in water and fish have improved considerably. Critical steps identified in this study are (i) the use of well-defined native standards for quantification, (ii) the use of mass-labelled internal standards (preferably one for each target compound) and (iii) minimization of matrix effects by a better clean up.

Acetylsalicylic acid as antifungal in Eremothecium and other yeasts.

Interesting distribution patterns of acetylsalicylic acid (ASA, aspirin) sensitive 3-hydroxy (OH) oxylipins were previously reported in some representatives of the yeast genus Eremothecium--an important group of plant pathogens. Using immunofluorescence microscopy and 3-OH oxylipin specific antibodies in this study, we were able to map the presence of these compounds also in other Eremothecium species. In Eremothecium cymbalariae, these oxylipins were found to cover mostly the spiky tips of narrowly triangular ascospores while in Eremothecium gossypii, oxylipins covered the whole spindle-shaped ascospore with terminal appendages. The presence of these oxylipins was confirmed by chemical analysis. When ASA, a 3-OH oxylipin inhibitor, was added to these yeasts in increasing concentrations, the sexual stage was found to be the most sensitive. Our results suggest that 3-OH oxylipins, produced by mitochondria through incomplete beta-oxidation, are associated with the development of the sexual stages in both yeasts. Strikingly, preliminary studies on yeast growth suggest that yeasts, characterized by mainly an aerobic respiration rather than a fermentative pathway, are more sensitive to ASA than yeasts characterized by both pathways. These data further support the role of mitochondria in sexual as well as asexual reproduction of yeasts and its role to serve as a target for ASA antifungal action.

The salivary gland and salivary enzymes of the giant waterbugs (Heteroptera; Belostomatidae).

The giant waterbugs are predators that utilize extra-oral digestion and are known to capture a wide variety of prey. Herein we describe the differences in salivary enzyme composition between large and small species of giant waterbug (Lethocerus uhleri, Lethocerinae and Belostoma lutarium, Belostomatinae, respectively). The saliva of L. uhleri contains 3 proteolytic enzymes and no amylase, while the salivary gland of B. lutarium produces 2 proteolytic enzymes and amylase. This fundamental difference in salivary enzyme composition correlates with the difference in diet preference between the Lethocerinae and Belostomatinae. Furthermore, we describe the ultrastructure of the salivary gland complex of B. lutarium and present data on the division of labor with respect to compartmentalization of enzyme production. Proteolytic enzymes are produced in the accessory salivary gland and amylase is produced in the main salivary gland lobe. This is the first reported evidence of protease production in the accessory salivary gland in the Heteroptera.

A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma.

OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline values of hemoglobin, leukocyte, and platelets were slightly lower in the amifostine group, but the mean percentual decrease of these parameters after each treatment cycle showed no difference between both arms. Symptoms of neurotoxicity remained absent in 40% PC vs. 49% PC + A cycles; sensory neurotoxicity grade I occurred in 45% vs. 48% and grade II in 12% PC vs. 2% of PC + A cycles (overall P < 0.001). Nausea grade II was reported in 2% vs. 6% (P = 0.007) and vomiting grade II in 1% of PC vs. 8% PC + A cycles (P < 0.001). Amifostine was temporarily interrupted in five patients due to hypotension, but no dose reductions were indicated. Quality of life questionnaires showed no difference in neurotoxicity scores between both study arms at treatment completion. The median progression-free survival was 16 vs. 22 months (n.s.) for PC and PC + A patients. In a pooled analysis of four randomized studies, amifostine diminished the risk of developing neurotoxicity grade II-III (Odds Ratio 0.3, 95% confidence interval 0.15-0.63, P < 0.05), but had no effect on the risk for bone marrow toxicity. CONCLUSION: Amifostine shows only minor but significant activity in diminishing neurotoxicity without preventing paclitaxel + carboplatin-induced bone marrow toxicity.

Determination of diuron and the antifouling paint biocide irgarol 1051 in Dutch marinas and coastal waters.

A sensitive LC-electrospray MS-MS method using off-line solid-phase extraction for the determination of diuron and Irgarol 1051 has been developed, enabling determination of both compounds at sub-ppt levels. Diuron and Irgarol 1051 are used as alternatives for tributyltin in antifouling paints that prevent growth on boats, and an increase in their application is anticipated because of the upcoming ban on tributyltin in 2003. In 2000, a survey was carried out to assess contamination with diuron and Irgarol 1051 of a number of Dutch marinas and coastal waters. Depending on the time of year, both compounds were encountered at levels higher than the maximum permissible concentrations of 430 and 24 ng/l for diuron and Irgarol 1051, respectively. Outside marinas at reference locations, concentrations were much lower, depending on the geographical situation and the nature of the water exchange with the environment related to tidal cycles. A seasonal influence was observed with highest levels in summer, corresponding to the yachting season for both compounds. For diuron, use in agriculture could have contributed to the high concentration encountered in surface waters.

Capillary electrophoresis with laser-induced fluorescence detection for fast and reliable apolipoprotein E genotyping.

The use of capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection for the rapid determination of apolipoprotein E (apoE) genotypes was studied. High resolution and sensitive detection of the concerned DNA restriction fragments was achieved using CE buffers with hydroxypropylmethylcellulose (HPMC) as sieving polymer and ethidium bromide (EB) as fluorescent intercalating agent. In order to achieve adequate resolutions in short analysis times, parameters such as concentration of HPMC and EB, separation voltage, and length and coating of the capillary were evaluated. Using a separation buffer with 0.8% (w/w) HPMC and 7 microM EB, characteristic DNA-fragment profiles could be obtained for all common apoE genotypes at an overall rate of ten samples per hour. The method allows direct injection of untreated PCR samples and the use of standard fused-silica capillaries which are effectively coated following a short, one-step rinse procedure. With a simple computerized algorithm based on migration-time ratios for pattern assignment, highly reliable apoE genotyping was achieved. Overall, in terms of speed, ease of use and objectivity the presented method provides a significant improvement over previously reported CE-based procedures for apoE genotyping.

Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer.

PURPOSE: To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. PATIENTS AND METHODS: Patients were randomly allocated to receive paclitaxel 175 mg/m(2) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2) or carboplatin (area under the plasma concentration-time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the hospital, whereas the carboplatin regimen was administered to outpatients. RESULTS: A total of 208 eligible patients were randomized. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin produced significantly less nausea and vomiting (P: <.01) and less peripheral neurotoxicity (P: =.04) but more granulocytopenia and thrombocytopenia (P: <.01). The overall response rate in 132 patients with measurable disease was 64% (84 of 132 patients), and in patients with elevated CA 125 levels at start, it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months. The small number of patients entered onto the study caused wide confidence intervals (CIs) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow conclusions about efficacy. CONCLUSION: Paclitaxel-carboplatin is a feasible regimen for outpatients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin.

Randomized phase II study of FEC day 1 + 8 and FEC day 1 in patients with advanced breast cancer.

BACKGROUND: Dose-intensive chemotherapy regimens without stem cell support have not resulted in an improved survival compared to standard dose regimens in patients with metastatic breast cancer. Combinations of an anthracycline, cyclophosphamide and 5 fluorouracil are still standard in such patients. The aim of this study was to investigate the two different schedules of epirubicin in a standard dose FEC regimen with respect to response and toxicity. MATERIALS AND METHODS: Patients were randomly assigned to receive a day 1 + 8 schedule (5FU and CTX 500mg/m2 day 1, epirubicin 40 mg/m2 day 1 and 8) or a day 1 schedule (5FU, CTX 500 mg/m2 and epirubicin 80 mg/m2 day 1), q day 21, both given without hematopoietic growth factors. A total of 104 eligible patients were analyzed, 52 in each arm. RESULTS AND CONCLUSIONS: A significantly higher relative dose-intensity was found for the day 1 schedule compared to the day 1 + 8 schedule. Although the trial was not set up to reliably detect a difference in response rate, this difference in relative dose-intensity in favour of the day 1 schedule does not suggest any improvement in response rate or duration of response for the day 1 schedule. Myelosuppression was severe in the day 1 + 8 schedule. We conclude that a day 1 + 8 FEC schedule has no advantage over a day 1 FEC schedule without hematopoietic growth factors in patients with metastatic breast cancer.

Development of the suprarostral plate of pipoid frogs.

The rostral region of nonpipoid tadpoles has two sets of cartilages, the cornua trabeculae and the suprarostral cartilages, whereas the rostral region in pipoid larvae is occupied by a single and continuous cartilage, the suprarostral plate. The homology of this region in pipoid and nonpipoids tadpoles has been controversial. We examined the early formation and development of the suprarostral plate using serially cross-sectioned specimens of Rhinophrynus, Xenopus, and Hymenochirus. We conclude that the cartilaginous structures present in the rostral area of pipoid and nonpipoid larvae are homologous. Furthermore, we found two different developmental patterns among pipoid larvae. The chondrocranium of Hymenochirus boettgeri is described and illustrated to understand its developmental pattern and because of its uniqueness among pipoid chondrocrania.

Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy.

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis.

The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but the combinations are expected to be equally effective. A disadvantage of the cisplatin-based regimen is that patients need to be admitted to the hospital. The carboplatin regimen can be administered to outpatients. We tested both combinations administered every 3 weeks in a randomized phase III study in patients with previously untreated epithelial ovarian cancer. An interim analysis for toxicity was performed in 145 patients shortly after study closure. We observed a difference in the incidence of nausea, vomiting, and neurotoxicity favoring the women treated with the carboplatin regimen, but this regimen caused more myelotoxicity. Maturation of the study is awaited before survival data can be analyzed and final conclusions can be drawn.

Elimination of intravenously administered radiolabelled antithrombin III and heparin in humans.

Antithrombin III was purified from normal plasma by DEAE-Sephadex chromatography and heparin affinity chromatography; the protein was subsequently radiolabelled with 125I. 125I-antithrombin III alone and 125I-antithrombin III in the presence of high affinity 35S-heparin fractions were injected into normal humans. 125I-radiolabel and protein bound 35S-radioactivity were followed separately. In semilogarithmic plots 125I-antithrombin III disappeared according to a double exponential curve with a half-life in the second phase of 56.8 hr in the absence of heparin and of 33.7 hr in the presence of heparin. Protein bound 35S-radioactivity disappeared much faster than the 125I-radiolabel. These data support the concept that heparin disappears as free heparin from the equilibrium heparin - antithrombin III in equilibrium heparin + antithrombin III. Immuno-reactive antithrombin III decreased from 100% to 85-90% immediately after injection of 125I-antithrombin III in the presence of heparin and returned to normal values within 30 min. This suggests that antithrombin III is transiently sequestered, possibly in trimolecular complexes consisting of antithrombin III, heparin and either lipases or other vascular bound proteins.

Elimination of high affinity heparin fractions and their anticoagulant and lipase activity.

High and low affinity heparin (HA and LA heparin) were prepared from commercial heparin by affinity chromatography to insolubilized antithrombin III. HA heparin was radiolabeled with 35S and subdivided by gel chromatography into high molecular weight (HMW, average 17,000-26,000 daltons), intermediate molecular weight (MMW, average 12,000-13,000 daltons), low molecular weight (LMW, average 5,000-7,000 daltons), and very low molecular weight (VLMW, average 4,600 daltons) fractions. The kinetics of lipolytic and anticoagulant activity and protein-bound radioactivity were studied after intravenous injection of these fractions. LA heparin failed to induce anticoagulant activity but released the hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL) activities normally. VLMW and LMW heparin failed to release both lipolytic enzymes and did not induce anticoagulant activity measurable by the activated partial thromboplastin time (APTT). A powerful anticoagulant effect was found in the anti-Xa assay, which disappeared according to a continuously concave curve in semilogarithmic plots, with elimination rates similar to those of the protein-bound radiolabel. The other heparin preparations induced all activities measured. Heparin anticoagulant activity estimated by the two assays disappeared following a convex curve, preceded by a rapid initial elimination phase in semilogarithmic plots. The disappearance rates of plasma protein-bound heparin radioactivity and heparin anticoagulant activity estimated by factor Xa inactivation were similar. Peak values of the two lipolytic activities were attained rapidly. H- TGL activity, as well as LPL activity, disappeared following convex curves in semilogarithmic plots, with elimination rates similar to those of plasma protein-bound heparin radioactivity. On the basis of these kinetics, we suggest that, after intravenous administration of heparin, the two lipolytic enzymes present in plasma are complexed with heparin, analogous to the heparin-antithrombin III complex. Finally, the kinetic data indicate that elimination of these activities is determined by the heparin part of the complexes, probably by removal of free heparin.

Controlled multicenter pilot study of urokinase- heparin and streptokinase in deep vein thrombosis.

Thirty-three patients with acute iliofemoral thrombosis were randomly assigned to three treatment groups in a pilot dose-ranging study of thrombolytic therapy in deep vein thrombosis. One group received tissue culture urokinase in a dose of 2,200 I.U./kg/hr, and a second group in a dose of 1,100 I.U./kg/hr following a loading dose of 4,400 I.U./kg given in ten min. Urokinase was administered for 12 hr periods, alternating with 12 hr periods of heparin. A third group received an initial dose of 250,000 I.U. of streptokinase in 20 min, followed by 100,000 I.U./hr. Treatment of all patients continued for three days. At the end of this period little improvement, evaluated by "blinded" interpretation of pre- and post-treatment phlebograms, was found in five out of ten of the higher-dose urokinase patients, seven out of eleven of lower-dosage urokinase patients, and six out of ten of streptokinase patients. Optional treatment for another three days showed little further improvement of urokinase-patients and moderate further improvement in the streptokinase-patients. Neither of the 2 dosage schemes at intermittent application of urokinase appeared to be advantageous. Urokinase treated patients experienced fewer adverse reactions.

Systemic fibrinolytic activity and inhibitor levels during treatment of deep vein thrombosis with urokinase and streptokinase.

In a prospective, randomized trial 33 patients with deep vein thrombosis were treated either with 2,200 or 1,100 IU/kg/h urokinase or with 100,000 IU/h streptokinase for at least 6 days. While streptokinase was given continuously, urokinase was administered intermittently (12 hr urokinase alternating with 12 hr heparin). Urokinase treatment resulted in a dose-dependent fibrinolytic state with shortening of the euglobulin clot lysis time, easily demonstrable amidolytic activity and moderate decrease of plasminogen. At the end of each urokinase-free interval the fibrinolytic activity had mostly faded, but was reproducibly elicited again by each new urokinase administration. Streptokinase immediately evoked the customary, intense fibrinolytic state, which progressively tapered off as plasminogen fell to 1% of its pretreatment concentration. In all treatment groups alpha-2-antiplasmin dropped to approximately 40% of its initial value during the first 12 hr with a further decrease to about 20% after 6 days. alpha-2-macroglobulin fell only moderately with either urokinase regimen, whereas it decreased progressively to 45% under streptokinase. While the fibrinolytic activity decreased under streptokinase over the 6-day infusion period, it appeared to increase with each successive urokinase infusion particularly with 1100 IU/kg/h. Thus the final euglobulin clot lysis times and the final fibrinogen concentrations were similar in all three treatment groups on the sixth day.