Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function.

Two hundred thirty-one patients with a first acute myocardial infarction were randomly allocated within 5 h after the onset of symptoms either to treatment with anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 min, or to conventional heparin therapy, 5,000 IU in a bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. One hundred twelve patients received APSAC and 119 received heparin within a mean period of 188 +/- 62 min after the onset of symptoms. Both groups were similar in age, location of the acute myocardial infarction, Killip functional class and time of randomization. Elective coronary arteriography was performed on an average of 4 +/- 1.2 days after initial therapy. Follow-up radionuclide angiography and thallium-201 single photon emission computed tomography were performed before hospital discharge. Infarct size was estimated from single photon emission computed tomography and expressed as a percent of total myocardial volume. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC group than in the heparin group. This was true for the entire study group (0.53 +/- 0.13 versus 0.47 +/- 0.12; p = 0.002) as well as for the subgroups of patients with anterior and inferior wall infarction (0.47 +/- 0.13 versus 0.40 +/- 0.11; p = 0.04 and 0.56 +/- 0.10 versus 0.51 +/- 0.11; p = 0.02, respectively). At 3 weeks, the difference remained significant for the anterior myocardial infarction subgroup. A significant 31% reduction in infarct size was found in the APSAC group (33% for the anterior infarction subgroup [p less than 0.05] and 16% for the inferior infarction subgroup [p = NS]). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -0.73, p less than 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparin-treated patients had died. In conclusion, the early infusion of APSAC in acute myocardial infarction produced a high early patency rate, significant limitation of infarct size and significant preservation of left ventricular systolic function, mainly in anterior wall infarction.

Use of grafts procured from organ transplant recipients.

BACKGROUND: Massive intracerebral bleeding may cause brain stem death in transplant (Tx) recipients early or late postTx. We addressed the question as to whether Tx recipients may safely be used as organ donors. In particular, it is feared that exposure to immunosuppressive drugs may render those organs unsuitable for Tx. METHODS: We reviewed two case reports of liver grafts procured from Tx patients. In addition, we conducted a survey within United Kingdom Transplant Support Service Authority (UKTSSA) to delineate the UK experience in that area. RESULTS: Donor 1 was an 50-year-old heart Tx recipient who became brain stem dead due to cerebral bleeding 8 months postTx. His liver was used in an 55-year-old patient with PBC who is alive and well more than 22 months postTx. Donor 2 was a 22-year-old kidney Tx patient who developed cerebral bleeding 4 years postTx. His liver was used in a 65-year-old patient with PBC who is doing well more than 27 months postTx. During the study period of 1989-1995, 13 organs (9 kidneys, 3 hearts, 1 liver) were procured from 6 brain stem dead Tx patients (3 long, 2 heart, and 1 kidney Tx patients). Seven recipients are enjoying satisfactory graft function 1 to 7 years postTx; one kidney Tx recipient was relisted 4 years postTx due to chronic rejection; five functionning grafts were lost to patient death; primary nonfunction was seen in one heart Tx recipient. CONCLUSIONS: Tx patients can be successfully used as organ donors. In particular, chronic exposure to immunosuppression is not per se a contraindication to donation. Tx physicians confronted with the rare and tragic event of brain stem death in a Tx patient should not a priori exclude these patients from donation.

Limitation of myocardial infarct size and preservation of left ventricular function by early administration of APSAC in myocardial infarction.

In cases of acute myocardial infarction (MI), it has been shown that preserving left ventricular function and limiting infarct size with early reperfusion of the occluded artery by means of a thrombolytic agent could eventually result in a reduced mortality rate. The aim of the APSIM study (anisoylated plasminogen streptokinase activator complex [APSAC] dans l'infarctus du Myocarde) was to demonstrate that early administration of APSAC in patients with recent acute MI could limit the infarct size and preserve left ventricular systolic function. In all, 231 patients with a first acute MI were randomly allocated to either APSAC (30 U over 5 minutes) or to conventional heparin therapy (5,000 IU in bolus injection) within 5 hours of the onset of symptoms. Of these patients, 112 received APSAC and 119 received heparin within a mean period of 188 +/- 62 minutes after the onset of symptoms. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC than in the heparin group. This was true for the entire population (0.53 +/- 0.13 vs 0.47 +/- 0.13, p = 0.002) as well as for the subgroups of anterior and inferior wall infarctions (0.47 +/- 0.13 vs 0.4 +/- 0.16, p = 0.004 and 0.56 +/- 0.11 vs 0.51 +/- 0.09, p = 0.02). At 3 weeks, the difference remained significant for patients with anterior MI.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B resistance of Aspergillus terreus in a murine model of disseminated aspergillosis.

The in-vivo activity of amphotericin B and itraconazole against a clinical isolate of Aspergillus terreus was determined in a murine model of disseminated aspergillosis. MICs of amphotericin B and itraconazole for the strain, determined by an NCCLS-based technique, were 2 microg/ml and 1 microg/ml, respectively. Mice infected intravenously were treated with either itraconazole (50 or 100 mg/kg/day) or amphotericin B 4.5 mg/kg/day for 10 days. Treatment with both doses of itraconazole significantly prolonged the survival rates compared with those for untreated mice. In comparison, mortality rate and median survival time were identical for mice treated with amphotericin B and for mice given no therapy, indicating that the strain was highly resistant to amphotericin B in this model. Analysis of sterol composition showed that the major sterol was ergosterol. This suggests that amphotericin B resistance was not related to a modified sterol profile.

In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. EBGA Network. European research group on Biotypes and Genotypes of Aspergillus fumigatus.

An animal model of disseminated aspergillosis was used to test the in-vivo activity of itraconazole against four isolates of Aspergillus fumigatus. Two reference isolates of A. fumigatus known to be resistant to itraconazole in vitro and in vivo were used as control isolates, and two new isolates were tested under the same conditions. For each isolate MICs for itraconazole and amphotericin B were determined by an NCCLS-based method. Mice infected intravenously were treated either with itraconazole 100 mg/ kg/day or amphotericin B 4.5 mg/kg/day for 10 days. Amphotericin B showed good in-vivo activity against all four isolates. For one strain, which had a low in-vitro MIC for itraconazole, in-vivo therapy with itraconazole prolonged the survival of mice and reduced fungal burdens in organs compared with untreated controls. In mice infected with a strain with a high MIC of >16 mg/L, itraconazole neither prolonged survival nor reduced fungal load in organs compared with controls. It is concluded that there is a relationship between MIC and treatment outcome in mice for A. fumigatus infection.

[Vitamin A deficiency in a rural population of Mauritania and absence of a correlation with urinary schistosomiasis]. / Carence en vitamine A dans une population rurale de Mauritanie et absence de corrélation avec la schistosomiase urinaire.

This work is part of a wider study on urinary schistosomiasis in a West African rural population and was devoted to the assessment of vitamin A deficiency and the analysis of relations between serum retinol levels and Schistosoma haematobium infection. The study took place in two villages located in a southeastern region of Mauritania (Hodh-El-Gharbi), a semi-arid zone struck by the Sahel drought. During the dry season 1985, 206 children between 1 and 15 years of age were randomly selected (single-stage cluster sampling), 81 from the first village, and 125 from the second. The following information was recorded: sex, age (or age group), symptoms of vitamin A deficiency, weight for height (NCHS reference), S. haematobium eggs count, vitamin A level and anti-schistosomiasis antibodies. In Kerkerat 4 children had eye signs of vitamin A deficiency and serum retinol concentration were found less than 100 micrograms/l in 8 subjects (10 +/- 3%) while 41 children had retinol serum concentration between 100 and 200 micrograms/l (50.6 +/- 5%). There was no difference between the age groups. In Limbehra most of children had serum retinol concentration greater than 200 micrograms/ml and no level less than 100 micrograms/l was found. In this village, children aged 10-15 years had a better retinol status than children under 10 years of age (chi 2 = 6.14, p less than 0.02). In both villages S. haematobium infection was not associated with a low serum retinol level. This study confirms that retinol deficiency is a public health problem in rural Mauritanian population, but keeping with other studies, there is no correlation with urinary schistosomiasis.

Effects on infarct size and left ventricular function of early intravenous injection of anistreplase in acute myocardial infarction. The APSIM Study Investigators.

A total of 231 patients suffering from a first acute myocardial infarction were randomly allocated within 4 hours following the onset of symptoms either to anistreplase or anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 minutes, or to conventional heparin therapy, 5000 IU in bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. A total of 112 patients received anistreplase and 119 received heparin within a mean period of 188 +/- 62 min following the onset of symptoms. Infarct size was estimated from single photon emission computerized tomography and expressed in percentage of the total myocardial volume. The patency rate of the infarct-related artery was 77% in the anistreplase group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the anistreplase group than in the heparin group (6 absolute percentage point difference). A significant 31% reduction in infarct size was found in the anistreplase group (33% for the anterior wall infarction subgroup [p less than 0.05] and 16% for the inferior wall infarction subgroup, NS). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -.73, p less than 0.01). In conclusion, early infusion of anistreplase in acute myocardial infarction produced a high early patency rate, a significant limitation of infarct size, and a significant preservation of left ventricular systolic function, mainly in the anterior wall infarctions.

Relationship between serum ferritin, erythrocyte protoporphyrin and transferrin saturation in Mauritanian free living children.

Serum ferritin, serum iron, total iron-binding capacity (TIBC) and erythrocyte protoporphyrin were measured in a group of 69 children (6.4 +/- 3.6 years) living in a rural area of Mauritania. The predictive value of low serum ferritin was calculated for each iron parameter. A serum ferritin value above 12 micrograms/l was present in 50.2% of children with abnormal serum iron, in 59.0% of those with abnormal TIBC, in 60.3% of those with abnormal transferrin saturation and in 60.0% of those with abnormal erythrocyte protoporphyrin. The percentages varied from 88.0 to 94.8% for a predictive value of serum ferritin of less than 50 micrograms/l. Nearly 35% of children had biochemical evidence of iron deficiency, i.e. 2 abnormal independent iron parameters or more, including serum ferritin of less than 12 micrograms/l. Nearly 32% had probable iron deficiency, i.e. 2 abnormal independent iron parameters, with a serum ferritin value between 13 and 50 micrograms/l.

[Anisoylated plasminogen streptokinase complex during the acute phase of myocardial infarction. Results of a multicenter double-blind study versus heparin]. / Le complexe streptokinase plasminogène acylé à la phase aiguë de l'infarctus du myocarde. Résultats d'une étude multicentrique en double aveugle versus héparine.

Two hundred and thirty-one patients admitted to hospital within 5 hours of the onset of symptoms of a primary myocardial infarction were randomised into 2 groups: one received thrombolytic therapy [anisoylated plasminogen streptokinase activator complex (APSAC): 30 IU in 5 minutes] and the other was given conventional heparin therapy (5,000 IU). Heparin was given to both groups 4 hours later (500 IU/kg/day); the APSAC (N = 119) was identical with respect to age, location of infarct, Killip classification, delay before randomisation (188 +/- 62 minutes). Coronary angiography and ventriculography were performed after 3.4 +/- 1.2 days, and angioscintigraphy and myocardial scintigraphy after 19 +/- 2.5 days to determine the size of the infarct and the quality of left ventricular function. Coronary patency was much higher in the APSAC group (77%) than the heparin group (37%) (p less than 0.001). The angiographic ejection fraction was significantly greater in the thrombolytic group than in the heparin group (53 +/- 13% vs 47 +/- 12%, p less than 0.002), the difference being statistically significant in the anterior and inferior infarct subgroups. At the third week, the difference remained significant in the anterior infarct subgroup: a 31 per cent reduction in necrosed myocardial mass was observed in the APSAC group (33% in anterior infarcts: p less than 0.05 and 16% in inferior infarcts: NS). The limitation of infarct size explained the smaller reduction in left ventricular systolic function (r = 0.73; p less than 0.01). The hospital and one year mortality was comparable in the two groups which was not surprising given the small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of thrombolytic agents on infarct size and left ventricle systolic function in myocardial infarction]. / Effet des thrombolytiques sur la taille de la nécrose et la fonction systolique ventriculaire gauche dans l'infarctus du myocarde.

The early intravenous administration of thrombolytic agents in the acute phase of myocardial infarction induces reperfusion of the artery responsible for the necrosis, thereby limiting the size of the infarct and preserving the left ventricular systolic function with consequent reduction of short- or long-term mortality. With the exception of urokinase, these effects have been demonstrated with all thrombolytic agents used so far, including streptokinase, plasminogen tissue activator and anistreplase. Owing to its special pharmacokinetic properties, the latest thrombolytic agent, formerly known as APSAC (anisoylated plasminogen streptokinase activator complex), provides a high arterial reperfusion rate with a low percentage of reocclusion. As a result, the mean size of the infarct is reduced by 31 per cent (36% in the case of anterior infarct), and the left ventricular systolic function is highly significantly preserved.

[Man-water contacts and urinary schistosomiasis in a Mauritanian village]. / Contacts homme-eau et schistosomiase urinaire dans un village mauritanien.

For the period September to December 1985, 1226 water contacts were recorded during 8 days of direct observation. Various activities were analysed in order to determine their responsibility in transmission. An index of exposure, allowing for duration of contact, body surface exposed and infectiousness of the water was calculated for each contact. Domestic contacts, primarily female, represented 62% of the observations but only 15% of total exposure. Conversely, contacts for recreational purposes mainly involved young boys and accounted for 14% of the observations and 70% of total exposure. Between 6 and 20 years of age the mean index of exposure by contact was higher in males than in females. Changing water contact behavior seems to be an unrealistic means of preventing transmission in the community studied. The most appropriate strategy of control would appear to be selective treatment of heavily infected individuals.

Comparison of a digestion-sedimentation technique with the Kato-Katz technique in the detection and quantification of S. mansoni eggs in light to moderate infections.

A comparison between a digestion-sedimentation technique (DST) and the Kato-Katz thick smear technique (KKT) in the detection and quantification of Schistosoma eggs in stool was carried out in 551 subjects. Specimen were collected one or two years after treatment with praziquantel from subjects living in a schistosomiasis endemic area of Mali. One hundred infections missed by the KKT were detected by the DST. Conversely, 35 infections missed by the DST were detected by the KKT (88% were light infections). More subjects were classified as lightly infected by the DST (p < 10(-3)) and more subjects were classified as moderately infected (101-400 epg) by the KKT (p = 0.02). The KKT produced higher counts than the DST among the youngest age group which was also the most infected. The principal advantage of the DST over the KKT was its better sensitivity to detect light infections resulting from a larger amount of stool processed.

Fluorogenic detection of viable Toxoplasma gondii.

In order to easily assess growth and destruction of Toxoplasma gondii in vitro, this report describes two double staining assays that both visualize live and dead organisms: acridine orange--ethidium bromide (AO-EB) and bisbenzimide (Hoechst 33258)--propidium iodide (B-PI). EB and PI were chosen for dead organisms staining while AO and B stain viable organisms. Thus, both double staining assays seem more informative than Giemsa staining or indirect immunofluorescence. They offer methods to study internal structure of the parasite as well as information on host-parasite relationships. Moreover, detection in culture are sensitive, easier, and less time consuming than previous methods. So, they should to be useful in strains behaviour analysis.

[Liver transplantation with a graft taken from a heart transplant patient who was brain-dead]. / Transplantation hépatique avec un greffon prélevé chez un greffé cardiaque en état de mort cérébrale.

The shortage of organ donors has led to progressive softening of selection criteria for organ donation. We report on hepatic transplantation in a 55-year-old woman with primary biliary cirrhosis, whose donor was a 50-year-old heart transplant recipient who became brain stem dead, due to cerebral bleeding 8 months after transplantation. An orthotopic liver transplantation was performed. The postoperative course was uneventful and the recipient was alive and had normal liver function after a 42-month follow-up. Analysis of the literature included ethical consideration, potential hepatotoxic effects of immunosuppressive drugs and modification of the graft immunogenicity. It confirms that transplanted patients should not be a priori excluded from organ donation.

[Cutaneous South-American Leishmaniasis. Parasitological and serological diagnosis by indirect immunofluorescence and enzyme linked immunoassay (ELISA). 94 cases]. / Leishmaniose cutanée sud-americaine. Diagnostic parasitologique et sérologique par immunofluorescence indirecte (IFI) et enzyme linked immuno assay (ELISA). A propos de 94 cas.

A parasitological (direct test and culture) and serological (IIF and ELISA) survey was carried out in 94 soldiers infested by a cutaneous South American leishmaniasis during a training in the guyanese forest. 52 p.c of the parasitological tests were positive, direct test being much more sensitive than cultures. By this technique, Leishmania Viannia guyanensis was detected 8 times, and Leishmania Viannia braziliensis twice. I.I.F. was negative in all cases because the utilization of a non-homologous antigen in the promastigote form and of the condition of its preparation. ELISA test utilizing the same antigen in a soluble form was specific and its sensitivity was 52 p.c. This technique was positive in 52 p.c of the cases, corroborating some diagnosis for which parasitological test was negative. 66 p.c of the total cases were confirmed.

Epidemiological survey of urinary schistosomiasis in southeastern Mauritania.

Nine villages in the Sahelian Western Hodh Region of Mauritania, West Africa, were surveyed for infection with Schistosoma haematobium. A total of 983 subjects were randomly selected (single stage cluster sampling) and they provided specimens. The populations of five villages were highly infected with prevalence rates exceeding 50% among children under 16 years of age and peak prevalences ranging from 75% to 100% for children 6-10 or 11-15 years old. Mean densities of infection reached their peak for the same age classes with geometric means ranging from 28 to 265 eggs/10 ml urine. No difference in prevalence or mean density was found between males and females after age adjustment. Frequency distributions of egg outputs were not random but aggregated. An indirect screening technique, based on urine analysis reagent strip findings, was able to identify 98% of the most infected subjects (greater than or equal to 50 eggs/10 ml urine).

Schistosoma haematobium infection in Mauritania: two years of follow-up after a targeted chemotherapy--a life-table approach of the risk of reinfection.

Reinfection pattern among 6- to 20-year-old subjects was studied over 24 months in two Mauritanian villages of intense Schistosoma haematobium infection after a targeted chemotherapy with praziquantel involving the whole community. Subjects received treatment according to the presence of haematuria/proteinuria and this indirect screening technique was able to identify 98-100% of the heavily infected subjects (50 + eggs/10 ml). The two villages differed with respect to their characteristics, quality of follow-up and reinfection pattern. The post-treatment 6-month cumulative incidence during the two transmission periods following the chemotherapy, estimated from a subset of 116 subjects, was 18.0% and 20.5%. Reinfection rates were higher among males (Cox-Mantel: P = 0.0015), among children 6-10 years of age than older (P = 0.0078) and among subjects with more than 50 eggs/10 ml of urine before treatment than subjects with a lower egg output (P = 0.009). A Cox proportional hazard regression model was fitted and confirmed that gender, age and pretreatment level of infection were predictors of the rate of reinfection but that there was no interaction between these predictors.

Acquired itraconazole resistance in Aspergillus fumigatus.

The antifungal susceptibility profiles of four ASPERGILLUS: fumigatus isolates, recovered at different times from a patient treated with itraconazole for a pulmonary ASPERGILLUS: infection, were evaluated. Itraconazole MICs against two pre-treatment isolates were 0.5 mg/L, whilst two later isolates, recovered after at least 4 months of itraconazole therapy, had itraconazole MICs of >16 mg/L. In vivo susceptibilities to itraconazole and amphotericin B were tested in a murine model of disseminated aspergillosis. Treatment efficacy was evaluated by examining mortality rates and qualitative cultures of brain and kidneys. Itraconazole therapy significantly prolonged survival of mice infected with the initial isolates as compared with untreated controls. The third isolate was only partially susceptible to itraconazole in vivo, and the fourth isolate was highly resistant. The four isolates were typed by random amplified polymorphic DNA (RAPD) with four different primers. RAPD patterns obtained with each of them were identical, suggesting that the same strain was recovered over time and had acquired resistance to itraconazole.