Primary repair of a completely ruptured intermediate bronchus after blunt chest trauma. Case report.

BACKGROUND: Tracheobronchial injury is rare and often has a fatal course. The incidence is estimated from 0.8% to 5% in the scenario of blunt or penetrating chest trauma. CASE PRESENTATION: A 54-year-old male was brought to the emergency department after falling off his bicycle, with impact on head and right shoulder. At pre-hospital assessment, the patient had a free airway, gasping respiration (oxygen saturation 92%) with reduced vesicular breathing. Multiple rib fractures are palpable bilaterally, with subcutaneous emphysema. Computed tomography (CT) showed a large right-sided pneumothorax and consolidated lung lobes. After insertion of two chest tubes on the right, a refractory pneumothorax with large air leakage remained present. Subsequently, a bronchoscopy was performed, confirming a complete rupture of the right intermediate bronchus. Urgent surgical debridement and primary repair with an end-to-end running suture was performed. Rib osteosynthesis was additionally performed bilaterally, because of a flail chest on the right side and penetrating bone fragment on the left side. Respiratory function recovered uneventfully. CONCLUSION: Airway injuries are uncommon but must always be suspected by the clinician during the early management of chest trauma. To prevent delayed diagnosis and potentially fatal outcome, low-threshold bronchoscopy is the diagnostic modality of choice to accurately confirm the lesion. Primary surgical repair remains the mainstay of the therapeutic management.

The European sea bass: a key marine fish model in the wild and in aquaculture.

The European sea bass (Dicentrarchus labrax L.) is a marine fish of key economic and cultural importance in Europe. It is now more an aquaculture than a fisheries species (>96% of the production in 2016), although modern rearing techniques date back only from the late 1980s. It also has high interest for evolutionary studies, as it is composed of two semispecies (Atlantic and Mediterranean lineages) that have come into secondary contact following the last glaciation. Based on quantitative genetics studies of most traits of interest over the past 10-15 years, selective breeding programs are now applied to this species, which is at the beginning of its domestication process. The availability of a good quality reference genome has accelerated the development of new genomic resources, including SNP arrays that will enable genomic selection to improve genetic gain. There is a need to improve feed efficiency, both for economic and environmental reasons, but this will require novel phenotyping approaches. Further developments will likely focus on the understanding of genotype-by-environment interactions, which will be important both for efficient breeding of farmed stocks and for improving knowledge of the evolution of natural populations. At the interface between both, the domestication process must be better understood to improve production and also to fully evaluate the possible impact of aquaculture escapees on wild populations. The latter is an important question for all large-scale aquaculture productions.

Effect of production quotas on economic and environmental values of growth rate and feed efficiency in sea cage fish farming.

In sea cage fish farming, production quotas aim to constrain the impact of fish farming on the surrounding ecosystem. It is unknown how these quotas affect economic profitability and environmental impact of genetic improvement. We combined bioeconomic modelling with life cycle assessment (LCA) to calculate the economic (EV) and environmental (ENV) values of thermal growth coefficient (TGC) and feed conversion ratio (FCR) of sea bass reared in sea cages, given four types of quota commonly used in Europe: annual production (Qprod), annual feed distributed (Qannual_feed), standing stock (Qstock), and daily feed distributed (Qdaily_feed). ENV were calculated for LCA impact categories climate change, eutrophication and acidification. ENV were expressed per ton of fish produced per year (ENV(fish)) and per farm per year (ENV(farm)). Results show that irrespective of quota used, EV of FCR as well as ENV(fish) and ENV(farm) were always positive, meaning that improving FCR increased profit and decreased environmental impacts. However, the EV and the ENV(fish) of TGC were positive only when quota was Qstock or Qdaily_feed. Moreover, the ENV(farm) of TGC was negative in Qstock and Qdaily_feed quotas, meaning that improving TGC increased the environmental impact of the farm. We conclude that Qstock quota and Qdaily_feed quota are economically favorable to a genetic improvement of TGC, a major trait for farmers. However, improving TGC increases the environmental impact of the farm. Improving FCR represents a good opportunity to balance out this increase but more information on its genetic background is needed to develop breeding programs improving FCR.

Viral encephalopathy and retinopathy in aquaculture: a review.

Viral encephalopathy and retinopathy (VER), otherwise known as viral nervous necrosis (VNN), is a major devastating threat for aquatic animals. Betanodaviruses have been isolated in at least 70 aquatic animal species in marine and in freshwater environments throughout the world, with the notable exception of South America. In this review, the main features of betanodavirus, including its diversity, its distribution and its transmission modes in fish, are firstly presented. Then, the existing diagnosis and detection methods, as well as the different control procedures of this disease, are reviewed. Finally, the potential of selective breeding, including both conventional and genomic selection, as an opportunity to obtain resistant commercial populations, is examined.

Economic values of growth and feed efficiency for fish farming in recirculating aquaculture system with density and nitrogen output limitations: a case study with African catfish (Clarias gariepinus).

In fish farming, economic values (EV) of breeding goal traits are lacking, even though they are key parameters when defining selection objectives. The aim of this study was to develop a bioeconomic model to estimate EV of 2 traits representing production performances in fish farming: the thermal growth coefficient (TGC) and the feed conversion ratio (FCR). This approach was applied to a farm producing African catfish (Clarias gariepinus) in a recirculating aquaculture system (RAS). In the RAS, 2 factors could limit production level: the nitrogen treatment capacity of the biofilter or the fish density in rearing tanks at harvest. Profit calculation includes revenue from fish sales, cost of juveniles, cost of feed, cost of waste water treatment, and fixed costs. In the reference scenario, profit was modeled to zero. EV were calculated as the difference in profit per kilogram of fish between the current population mean for both traits (µt) and the next generation of selective breeding (µt+Δt) for either TGC or FCR. EV of TGC and FCR were calculated for three generations of hypothetical selection on either TGC or FCR (respectively 6.8% and 7.6% improvement per generation). The results show that changes in TGC and FCR can affect both the number of fish that can be stocked (number of batches per year and number of fish per batch) and the factor limiting production. The EV of TGC and FCR vary and depend on the limiting factors. When dissolved NH3-N is the limiting factor for both µt and µt+Δt, increasing TGC decreases the number of fish that can be stocked but increases the number of batches that can be grown. As a result, profit remains constant and EVTGC is zero. Increasing FCR, however, increases the number of fish stocked and the ratio of fish produced per kilogram of feed consumed ("economic efficiency"). The EVFCR is 0.14 €/kg of fish, and profit per kilogram of fish increases by about 10%. When density is the limiting factor for both µt and µt+Δt, the number of fish stocked per batch is fixed; therefore, extra profit is obtained by increasing either TGC, which increases the annual number of batches, or by decreasing FCR, which decreases annual feed consumption. EVTGC is 0.03 €/kg of fish and EVFCR is 0.05-0.06 €/kg of fish. These results emphasize the importance of calculating economic values in the right context to develop efficient future breeding programs in aquaculture.

Genotype by diet interactions in European sea bass (Dicentrarchus labrax L.): Nutritional challenge with totally plant-based diets.

Aquaculture of carnivorous species has strongly relied on fish meal and fish oil for feed formulation; however, greater replacement by terrestrial plant-based products is occurring now. This rapid change in dietary environment has been a major revolution and has to be taken into consideration in breeding programs. The present study analyzes potential consequences of this nutritional tendency for selective breeding by estimating genetic parameters of BW and growth rates estimated by the thermal growth coefficient (TGC) over different periods with extremely different diets. European sea bass (Dicentrarchus labrax L.) from a factorial cross (1,526 fish) between 25 sires and 9 dams were used to estimate heritabilities and genotype by diet interaction. Starting 87 d after fertilization (2.5 g), one-half of the sea bass were fed a diet containing marine products (M), and the other one-half were fed a totally plant-based (PB) diet (without any fish meal or fish oil). The fish were individually tagged, reared in a recirculated system, and genotyped at 13 microsatellites to rebuild parentage of individuals. Body weight and TGC were measured for 335 d until fish fed the M diet reached 108.3 g of BW. These traits were significantly less in fish fed the PB diet (P<0.05) in the very first stages after the dietary shift, but the difference in TGC between diets rapidly disappeared (P>0.1). Survival was significantly less in fish fed the PB diet (PB=64.7%, M=93.7% after 418 d, P<0.05). This work identified moderate heritabilities (0.18 to 0.46) for BW with both diets and high genetic correlations between diets (0.78 to 0.93), meaning low genotype by diet interactions, although diets were extremely different. Heritabilities of TGC (0.11 to 0.3) were less than for BW as well as genetic correlations between diets (0.43 to 0.64). Using such extremely different diets, predicted BW gains in different scenarios indicated that selecting fish for growth on a marine diet should be the most efficient way to increase growth on plant-based diets, meaning that, in this case, indirect selection should be more efficient than direct selection.

Regulation of FADS2 expression and activity in European sea bass (Dicentrarchus labrax, L.) fed a vegetable diet.

Supplies of marine fish oils are limited, and continued growth in aquaculture production dictates that lipid substitutes in fish diets must be used without compromising fish health and product quality. In this study, the total substitution of a fish meal and fish oil by a blend of vegetable meals (corn, soybean, wheat and lupin) and linseed oil in the diet of European sea bass (Dicentrachus labrax) was investigated. Two groups of European sea bass were fed with fish diet (FD) or vegetable diet (VD) for 9months. VD, totally deprived of eicosapentaenoate (EPA; 20:5n-3) and docosahexaenoate (DHA; 22:6n-3), revealed a nutritional deficiency and affected growth performance. Whilst VD induced a significant increase in fatty acid desaturase 2 (FADS2) and sterol binding regulatory element-binding protein 1 (SREBP-1) mRNA levels, the desaturation rate of [1-(14)C]18:3n-3 into [1-(14)C]18:4n-3, analysed in microsomal preparations using HPLC method, did not show an upregulation of FADS2 activities in liver and intestine of fish fed VD. Moreover Western-blot analysis did not revealed any significant difference of FADS2 protein amount between the two dietary groups. These data demonstrate that sea bass exhibits a desaturase (FADS2) activity whatever their diet, but a post-transcriptional regulation of fads2 RNA prevents an increase of enzyme in fish fed a HUFA-free diet. This led to a lower fish growth and poor muscle HUFA content.

Physiological mechanisms underlying a trade-off between growth rate and tolerance of feed deprivation in the European sea bass (Dicentrarchus labrax).

The specific growth rate (SGR) of a cohort of 2000 tagged juvenile European sea bass was measured in a common tank, during two sequential cycles comprising three-weeks feed deprivation followed by three-weeks ad libitum re-feeding. After correction for initial size at age as fork length, there was a direct correlation between negative SGR (rate of mass loss) during feed deprivation and positive SGR (rate of compensatory growth) during re-feeding (Spearman rank correlation R=0.388, P=0.000002). Following a period of rearing under standard culture conditions, individuals representing 'high growth' phenotypes (GP) and 'high tolerance of feed deprivation' phenotypes (DP) were selected from either end of the SGR spectrum. Static and swimming respirometry could not demonstrate lower routine or standard metabolic rate in DP to account for greater tolerance of feed deprivation. Increased rates of compensatory growth in GP were not linked to greater maximum metabolic rate, aerobic metabolic scope or maximum cardiac performance than DP. When fed a standard ration, however, GP completed the specific dynamic action (SDA) response significantly faster than DP. Therefore, higher growth rate in GP was linked to greater capacity to process food. There was no difference in SDA coefficient, an indicator of energetic efficiency. The results indicate that individual variation in growth rate in sea bass reflects, in part, a trade-off against tolerance of food deprivation. The two phenotypes represented the opposing ends of a spectrum. The GP aims to exploit available resources and grow as rapidly as possible but at a cost of physiological and/or behavioural attributes, which lead to increased energy dissipation when food is not available. An opposing strategy, exemplified by DP, is less 'boom and bust', with a lower physiological capacity to exploit resources but which is less costly to sustain during periods of food deprivation.

Spermatozoal competition in common carp (Cyprinus carpio): what is the primary determinant of competition success?

The percentage of sperm motility (92-100%), spermatozoan velocity (112-163 microm.s(-1)) and control hatching rates (83-96%) were evaluated for each of six gold and five green male common carp (Cyprinus carpio). In all 30 possible paired combinations of sperm-competition tests, hatching rates of 90-97% were achieved. The mean percentage of offspring sired was strongly influenced by the male used (P < 0.001, R2 = 0.91). The best male sired an average of 88% of the offspring in its competition tests, and the worst male sired only 5%. Spermatozoan-quality parameters could explain only part of the variation in male competitive ability. The male effects alone explained 91.4% of the observed variance, consisting of 17.1% explained by spermatozoan motility and 32.5% by control hatching rates in single fertilizations. Undetermined male effects explained 41.8%. The velocity of spermatozoa had no effect on the outcome of sperm competition. Neither was there any link between spermatozoan velocity and hatching rate in a control hatching test, whereas there was an effect of motility on hatching rate in this same test.

Transplantation tolerance and autoimmunity after xenogeneic thymus transplantation.

Successful grafting of vascularized xenografts (Xgs) depends on the ability to reliably induce both T cell-independent and -dependent immune tolerance. After temporary NK cell depletion, B cell suppression, and pretransplant infusion of donor Ags, athymic rats simultaneously transplanted with hamster heart and thymus Xgs developed immunocompetent rat-derived T cells that tolerated the hamster Xgs but provoked multiple-organ autoimmunity. The autoimmune syndrome was probably due to an insufficient development of tolerance for some rat organs; for example, it led to thyroiditis in the recipient rat thyroid, but not in simultaneously transplanted donor hamster thyroid. Moreover, grafting a mixed hamster/rat thymic epithelial cell graft could prevent the autoimmune syndrome. These experiments indicate that host-type thymic epithelial cells may be essential for the establishment of complete self-tolerance and that mixed host/donor thymus grafts may induce T cell xenotolerance while maintaining self-tolerance in the recipient.

Immunomodulatory effects of pretransplant donor blood transfusion on T-cell-independent xenoreactive immunity.

BACKGROUND: Pretransplant blood transfusions have beneficial effects on both clinical and experimental allograft survival. In the present study, we examined whether pretransplant hamster blood transfusions (pHBT) alone or together with peritransfusion immunosuppressive strategies designed to target B cells and/or natural killer (NK) cells, could modulate T cell-independent (T-I) xenoreactivity in athymic nude rats. METHODS: Hamster or mouse hearts were heterotopically xenotransplanted into untreated or treated athymic nude rats receiving either pHBT, anti-B cell or anti-NK cell therapy alone or their combinations. Xenoreactive antibodies (xAbs) and the percentage of NK cells were analyzed by FACScan analysis. NK cytotoxicity was measured by a standard 4 hr 51Cr release assay. Xenografts (Xgs) were examined by hematoxylin-eosin (H&E), by light microscopic method with Masson's trichrome and orcein staining, by immunofluorescent staining for immunoglobulin M and C3 deposition, and by immunohistochemical staining for infiltration of NK cells and macrophages (Mphis). RESULTS: In 1 of 6 rats given pHBT alone 2 weeks before receiving hamster xenografts, Xg survival was prolonged to 55 days compared with 3.0+/-1.2 days in the other 5 animals and with 3.0+/-0.6 days in untreated animals. In the 55 days, surviving Xg infiltration of Mphis and NK cells was seen together with severe signs of chronic rejection, such as fibrosis and obliterative vasculopathy. The addition of the anti-B cell immunosuppressant MNA715 (malononitriloamide x920715, 20 mg/kg/day) from day -14 to day +14 or of 100 microL of rabbit anti-asialo GM1 serum ([anti-ASGM1] an NK cell depleting antibody) on day -14 resulted in a significant and species-specific prolongation of the survival of hamster Xgs, respectively 59.8+/-9.6 days and 58.2+/-14.7 days (P<0.001 vs. control group), but not of mouse heart Xgs that were rejected in a normal tempo. All prolonged hamster Xgs were infiltrated with Mphis and NK cells and developed severe lesions of chronic rejection, such as fibrosis and obliterative vasculopathy. In contrast, MNA715 or anti-ASGM1 alone had no effect on Xg survival (4.8+/-1.7 days and 2.7+/-0.6 days, respectively). Combined MNA715/anti-ASGM1 treatment only moderately promoted Xg survival (10+/-5.0 days; P<0.001). A simultaneous administration of pHBT, MNA715, and anti-ASGM1 induced indefinite and species-specific Xg survival in all recipients. In vivo and in vitro studies demonstrated that both T-I B cell and NK cell species-specific xenotolerance were achieved. CONCLUSIONS: Pretransplant blood transfusion may have a species-specific immunomodulatory effect on T-I xenoreactivity. This effect is further enhanced by a temporary co-administration of MNA715 or by a single injection of anti-ASGM1. A combination of pHBT, MNA715, and anti-ASGM1 induces species-specific T-I xenotolerance.

Effect of staphylococcal enterotoxin B injection on the development of experimental autoimmune encephalomyelitis: influence of cytokine and inducible nitric oxide synthase production.

Possible mechanisms involved in the protective effect of staphylococcal enterotoxin B (SEB) injection on the subsequent development of experimental autoimmune encephalomyelitis (EAE) were investigated. Only partial clonal deletion and anergy of Vbeta8 + T-lymphocytes were documented after myelin basic protein immunization in SEB injected mice. Brain permeability was not influenced. Within the brain or during in vitro rechallenge assays SEB protected mice produced significantly more IL-10, IL-4, TNF-alpha and iNOS. It is suggested that the immune deviating effect of SEB may be involved in its EAE protective effect.

Irradiation of fish embryos prior to blastomere transfer boosts the colonisation of their gonads by donor-derived gametes.

Blastomere transplantation into fish blastula embryos results in somatic chimeras, which generally provide null or a small proportion of gametes derived from the donor. This may partly explain why none of the ES-like cell lines established from fish embryos has contributed to the germline of chimeras when transplanted at the blastula stage. Here, we report that a moderate gamma-irradiation of recipient embryos, followed by transplantation of dispersed blastomeres, considerably enhances the proportion of donor-derived gametes (53% versus 5% in average). In fish, the resulting protocol should maximise the pluripotency level measured in vivo for embryonic cell lines and for cultured germ cells.

A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor TNP-470.

Hemangiomas represent the most frequent tumors of infancy. However, the pathogenesis of these tumors is still largely unknown, and current treatment of juvenile hemangiomas remains unsatisfactory. Here we present a novel animal model to study proliferating hemangiomas and to evaluate the effect of angiostatic compounds on their growth. Intraperitoneal (i.p.) infection of 4-day-old rats with murine polyomavirus resulted in the development of multiple cutaneous, intramuscular (i.m.), and cerebral hemangiomas with 100% frequency. Histological examination of the brain revealed the formation of immature lesions as soon as 4 days postinfection (p.i.). The subsequent exponential growth of the hemangiomas, both in number and size, was associated with severe hemorrhage and anemia. The cerebral, cutaneous, and i.m. lesions consisted of blood-filled cysts, histologically similar to human cavernous hemangiomas and stained positive for proliferating cell nuclear antigen, urokinase-type plasminogen activator, and vascular endothelial growth factor. Mature cerebral hemangiomas also expressed von Willebrand factor. Cerebral lesions caused death of the untreated animals within 19.2 +/- 1.1 days p.i. Remarkably fewer and smaller hemangiomas developed in animals that had been treated s.c. with the angiogenesis inhibitor TNP-470. Accordingly, TNP-470 (50 mg/kg), administered twice a week from 3 days p.i., significantly delayed tumor-associated mortality [mean day of death, 28.2 +/- 3.3 (P < 0.001)]. Even if therapy was initiated when cerebral hemangiomas were already macroscopically visible (i.e., 9 days p.i.), a significant delay in hemangioma-associated mortality was observed. Also, the IFN-inducer polyinosinic-polycytidylic acid caused a delay of 9 days (P < 0.005) in tumor-associated mortality when administered i.p. at 5 mg/kg, twice a week, starting at day 3 p.i. The model described here may be useful for investigating (a) the angiogenic mechanism(s) underlying hemangioma progression; and (b) the effect of anti-angiogenic compounds on vascular tumor growth.

Late acute rejection and subclinical noncompliance with cyclosporine therapy in heart transplant recipients.

BACKGROUND: Although noncompliance with immunosuppressive medication is recognized as a critical behavioral risk factor for late acute rejection episodes and graft loss after transplantation, little is known about the degree of subclinical cyclosporine noncompliance, its associated risk for acute late rejection episodes (>1 year after transplantation), and its determinants in heart transplant recipients. METHODS: The convenience sample of this longitudinal study included 101 European heart transplant recipients (87 men and 14 women), with a median age of 56 (Q1 = 50, Q3 = 61) and a median posttransplantation status of 3 (range 1 to 6) years. Subclinical cyclosporine noncompliance was measured during a 3-month period with electronic event monitoring. Selected sociodemographic, behavioral, cognitive, emotional, health, and treatment-related determinants of medication noncompliance were measured by using instruments with established psychometric properties or by patient interviews. With the use of iterative partitioning methods of cluster analysis, including nonstandardized electronic event monitoring compliance parameters, patients were categorized by degree of subclinical cyclosporine noncompliance into a 3-cluster solution. RESULTS: Overall compliance was high, with a median medication taking compliance of 99.4%. The 3 derived clusters, that is, excellent compliers (84%), minor subclinical noncompliers (7%), and moderate subclinical noncompliers (9%), differed significantly by degree of subclinical noncompliance (p < .0001) and showed a 1.19%, 14.28%, and 22.22% incidence of late acute rejections (p = .01), respectively. The 3 groups also differed in terms of former medication noncompliance (p = .02), appointment noncompliance (p = .03), and perceived self-efficacy with medication taking (p = .04). CONCLUSIONS: Although in absolute numbers cyclosporine compliance in this sample was high, minor deviations from dosing schedule were associated with an increased risk for acute late rejection episodes. This suggests a pivotal role of patient compliance in successful long-term outcome after transplantation.

Potent inhibition of hemangioma formation in rats by the acyclic nucleoside phosphonate analogue cidofovir.

The acyclic nucleoside phosphonate analogue cidofovir elicited a marked protection against hemangioma growth in newborn rats that had been infected i.p. with a high titer of murine polyomavirus. Untreated, infected rats developed cutaneous, i.m., and cerebral hemangiomas associated with severe hemorrhage and anemia leading to death within 3 weeks postinfection (p.i.). s.c. treatment with cidofovir at 25 mg/kg, once a week, resulted in a complete suppression of hemangioma development and associated mortality when treatment was initiated at 3 days p.i. (100% survival compared with 0% for the untreated animals). Cidofovir still afforded 40% survival and a significant delay in tumor-associated mortality when treatment was started at a time at which cerebral hemangiomas were already macroscopically visible (i.e., 9 days p.i.). Infectious virus or viral DNA was undetectable in the brain at different times p.i. as assessed by means of (a) a DNA-DNA hybridization assay and (b) titration of the brain for infectious virus content, indicating that there was no viral replication in murine polyomavirus-infected rats. Moreover, a semiquantitative PCR for viral protein 1 DNA revealed that the amount of viral protein 1 DNA declined with time after infection to become virtually undetectable at 18 days p.i. Therefore, an antitumor or antiangiogenic effect, rather than inhibition of viral replication, may be the reason for the inhibitory activity of cidofovir in this model. Cidofovir may thus be further explored for the treatment of vascular tumors and, in particular, life-threatening juvenile hemangiomas.

Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine in choriocarcinoma-bearing rats.

The acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective antiretroviral agent which is currently evaluated in its oral prodrug form, bis(POM)PMEA (adefovir dipivoxil), in phase II and III clinical trials in human hepatitis B virus (HBV)- and human immunodeficiency virus (HIV)-infected individuals, respectively. We have now found that PMEA is also a potent inhibitor of growth of the highly aggressive choriocarcinoma tumor arising from rat choriocarcinoma RCHO cells grafted under the kidney capsule of syngeneic WKA/H rats. In untreated rats, massive invasive RCHO tumors, covering the whole surface of the kidney and resulting in a marked enlargement of the kidney, were observed at day 10 after tumor cell grafting. Daily treatment with PMEA at 25 mg/kg/day afforded a marked reduction in tumor size (i.e., smaller tumors and slight, if any, enlargement of the kidney). Increasing the PMEA dose to 50, 100 or 250 mg/kglday resulted in a gradual increase of the antitumor effect of the compound. At the highest dose tested, i.e., 250 mg/kg/day, PMEA completely suppressed tumor growth. The antitumor activity of PMEA persisted for at least 10 days after termination of drug treatment. In addition, delayed treatment with PMEA at a dose of 200 mg/kg/day, started at a time point where choriocarcinoma tumors had already developed, stopped further growth and even induced regression of the tumors. PMPA, a closely related structural analogue of PMEA, failed to inhibit choriocarcinoma tumor growth. This observation points to the specificity of PMEA as an antitumor agent. In view of our findings, the therapeutic potential of PMEA for the treatment of neoplastic diseases appears to merit further investigation.