Surgery and granulocyte transfusions for life-threatening infections in chronic granulomatous disease.

We report two patients with chronic granulomatous disease (CGD) and life-threatening infections: a 10 10/12-year-old boy had Aspergillus fumigatus spondylitis with destruction of the 11th vertebral body and paravertebral abscess formation, and an 8 5/12-year-old boy had multiple Staphylococcus aureus hepatic abscesses with subphrenic abscess formation. Both patients failed to respond to intense antimicrobial therapy but showed a remarkable recovery following surgical drainage combined with granulocyte transfusions. These results suggest that antimicrobial therapy and surgical drainage followed by granulocyte transfusions may be the ideal mode of treatment for severe infections in patients with CGD.

Biocompatibility of an x-shaped zirconium implant in deep sclerectomy in rabbits.

BACKGROUND: The aim of this study was to evaluate the mid-term biocompatibility of a new x-shaped implant made of zirconium in an animal model of glaucoma surgery. METHODS: Preoperatively, ultrasound biomicroscopy (UBM), intraocular pressure (IOP) and outflow facility (OF) data were acquired. Upon surgery, one eye was chosen randomly to receive an implant, while the other received none. Ten rabbits went through a 1-, 2-, 3-, 4- and 6-month follow-up. IOP was measured regularly, UBM performed at 1, 3 and 6 months after surgery. At the end of the follow-up, OF was again measured. Histology sections were analyzed. RESULTS: For both groups IOP control was satisfactory, while OF initially increased at month 1 to resume preoperative values thereafter. Eyes with implants had larger filtration blebs which decreased faster than in eyes without the implant. Drainage vessel density, inflammatory cell number and fibrosis were higher in tissues near the implant. CONCLUSIONS: The zirconium implant initially promoted the positive effects of the surgery (IOP control, OF increase). Nevertheless, after several months, foreign body reactions and fibrosis had occurred on some implants that restrained the early benefit of such a procedure. Modifications of the zirconium implant geometry could enhance the overall success rate.

Scanning Electron Microscopy of Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae)

Lagochilascaris minor Leiper, 1909 is a parasitic nematode with its biological cycle still unknown, even though it was found in humans, domestic and silvatic animals. Adult worms, collected by surgical drainage from a human patient from the State of Pará, Brazil, were micrographed using a scanning electron microscope. Morphological aspects of males and females such as cephalic structures, caudal papillae and cuticular patterns were analyzed and compared with the previous descriptions adding new data for the identification of this species.

Endothelial nitric oxide synthase gene transfer restores endothelium-dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E-deficient mice.

Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP-1 downregulation. Early stages of arteriosclerosis are associated with reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1 inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE(-/-)) mice. Endothelium-dependent relaxations were impaired in carotid arteries instilled with a noncoding adenoviral vector but were restored by eNOS gene transfer (p < 0.01). A perivascular collar was placed around the common carotid artery to accelerate lesion formation. eNOS gene transfer reduced lesion surface areas, intima/media ratios, and macrophage contents in the media at 5-week follow-up (p < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation. In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and inhibits lesion formation in ApoE(-/-) mouse carotids. Further studies are needed to assess whether vasoprotection is maintained at later disease stages and to evaluate the long-term efficacy of eNOS gene therapy for primary arteriosclerosis.

New bench test for venous cannula performance assessment.

Cannula design is of prime importance for venous drainage during cardiopulmonary bypass (CPB). To evaluate cannulas intended for CPB, an in vitro circuit was set up with silicone tubing between the test cannula encased in a movable preload reservoir and another static reservoir. The pressure-drop (DeltaP) value (P-drainage - P-preload) was measured using Millar pressure transducers. Flow rate (Q) was measured using an ultrasound flowmeter. Data display and data recording were controlled using a LabView application, custom made particularly for our experiments. Our results demonstrated that DeltaP, Q, and cannula resistance (DeltaP/Q) values were significantly decreased when the cannula diameter was increased for Smart and Medtronic cannulas. Smartcanula showed 36% and 43% less resistance compared to Medtronic venous and Medtronic femoral cannulas, respectively. The cannula shape (straight- or curved-tips) did not affect the DLP cannula resistance. Out of five cannulas tested, the Smartcanula outperforms the other commercially available cannulas. The mean (DeltaP/Q) values were 3.3 +/- 0.08, 4.07 +/- 0.08, 5.58 +/- 0.10, 5.74 +/- 0.15, and 6.45 +/- 0.15 for Smart, Medtronic, Edwards, Sarns, and Gambro cannulas, respectively (two-way ANOVA, p < 0.0001). In conclusion, the present assay allows discrimination between different forms of cannula with high or low lumen resistance.

Solitary fibrous tumor of the lateral ventricle: CT appearances and pathologic correlation with follow-up.

Intracranial solitary fibrous tumors are rare, and intraventricular fibrous tumors are even more unusual. We report a case of solitary fibrous tumor in the region of trigone and body of the left lateral ventricle and discuss the clinical presentation, CT characteristics, and histopathologic features with 1-year follow-up. We speculate that the tumor arose from the perivascular connective tissue of the choroid plexus.

Estudi amb georadar del jaciment arqueològic de Lady Field (Woolston Manor Farm, Somerset, Gran Bretanya)

Projecte de recerca elaborat a partir d’una estada al University of Bristol, Gran Bretanya, durant agost i setembre del 2007. Els objectius del projecte d’estudi del jaciment de Lady Field (Woolston Manor Farm, Somerset, Gran Bretanya) eren, bàsicament, tres: en primer lloc, posar en pràctica els coneixements teòrics assolits durant la formació en prospecció geofísica; en segon lloc, aportar informació complementària a la aportada per la prospecció tradicional i el sondeig amb gradiòmetre magnètic efectuades prèviament per l’equip investigador del centre, arribant a definir millor les estructures poc definides per l’altre sistema i, finalment, obtenir un cas d’estudi sobre un jaciment medieval a Gran Bretanya, on les condicions geològiques i climàtiques, que afecten els resultats de la prospecció, són diferents a les del nostre país. Aquests objectius s’han assolit, ja que s’ha pogut portar a terme una prospecció de camp amb el sistema de georadar, processar les dades i obtenir-ne dades de qualitat i obtenir informació útil i rellevant de cara a la definició de les restes detectades, una vegada feta la interpretació. Els resultats mostren l’aparició en el subsòl del jaciment de quatre possibles fases d’ocupació, entre les que destaquen un moment amb possibles restes d’una antiga xarxa urbana, treballs agrícoles o un sistema de drenatge del terreny. Finalment l’estudi ha pogut constatar que la prospecció amb GPR en aquestes condicions geològiques és possible, tot i que les climàtiques –essencialment la pluja i la humitat del sòl- suposen complicacions a l’hora d’adquirir dades de forma segura per la maquinària i per la qualitat de les dades.

Chemotherapy induces tumor metastasis and dormancy

Chemotherapy is widely used as a systemic treatment modality in cancer patients and provides survival benefits for a significant fraction of treated patients H However, some patients suffer from cancer relapse and rapidly progress to metastasis, suggesting that following chemotherapy their residual tumor developed a more aggressive phenotype 4 5. Although some molecular mechanisms involved in chemo-resistance and chemotherapy-induced metastatic relapse have been reported, more investigations and understanding of these processes are necessary before any translation into the clinic might be considered. By using the syngeneic metastatic 4T1 murine breast cancer model, we observed that chemotherapy treatment and selection of chemotherapy-resistant cancer cells in vitro can induces two opposite phenotypes: a dormant one and a relapsing-metastatic one. Previous studies in our laboratory demonstrated that irradiation of mammary gland promotes tumor metastasis, at least in part, by inducing the recruitment of CD11b+ cells to both the primary tumor and the lungs at a pre-metastatic stage. In this study we found that CD11b+ cells may also play important roles in chemotherapy-induced tumor metastasis and dormancy in vivo. Tumor cells expressing the stem cell marker Sca-1 were enriched by chemotherapy treatment in vitro, as well as in tumor metastasis in vivo. Furthermore, tumor-derived CD11b+ cells were capable to maintain and expand this population in vitro. These results suggest that the expansion of a tumor cell population with stem cell features might be a mechanism by which chemotherapy induces metastasis. On the other hand, the same drug treatment in vitro generated resistant cells with a dormant phenotype. Dormant tumor cells were able to induce an in vivo immune- inflammatory response in the draining lymph node, which is normally absent due to the immunosuppressive effects of tumor-recruited myeloid derived- suppressor cells (MDSCs). Genome-wide gene expression analysis revealed the enrichment of invasion and metastasis-related genes in the relapsing metastatic tumor cells and immune response-related genes in the dormant tumor cells. Interestingly, CD11b+ cells derived from the microenvironment of growing-metastatic tumors, but not CD11b+ cells derived from the spleen of tumor-free mice, were able to instigate outgrowth of dormant tumor cells in vivo. Also, dormant cells formed growing and metastatic tumors when injected into immune-compromised NGS mice. These results point to a role of chemotherapy in enabling treated tumor cells to acquire immune response-inducing capabilities, while impairing the recruitment of CD11b+ cells and their differentiation into an immune-suppressive cell. The molecular mechanisms underneath these effects are being further investigated. In conclusion, results obtained in this model indicate that chemotherapy can induce a dormant phenotype in cancer cells and that this state of dormancy can be broken by MDSCs educated by relapsing tumors. Understanding the mechanism beyond these effects, in particular unraveling the genetic or epigenetic determinants of dormancy vs relapse, might open the way to therapies aimed and maintaining residual cells escaping chemotherapy in a state of sustained dormancy. - La chimiothérapie est un traitement systémique largement utilisé chez les patients cancéreux qui donne un avantage de survie significatif pour une bonne partie de patients traités (1-3). Cependant, certains patients souffrent d'une rechute et progressent ensuite vers la métastase. Ceci suggère que leur tumeur résiduelle a développé un phénotype agressif suite à la chimiothérapie (4-5). Bien que certains mécanismes moléculaires impliqués dans la chimiorésistance et la rechute métastatique ont été identifiés, d'avantage d'études sont nécessaires afin de mieux comprendre ce phénomène et de développer des nouvelles thérapies cliniques. En utilisant un modèle syngénique de cancer du sein métastatique chez la sourie (4T1), nous avons observé que la sélection des cellules cancéreuses résistantes à la chimiothérapie in vitro peut induire deux phénotypes opposés: un phénotype de dormance et un phénotype de progression métastatique. Une étude précédente issue de notre laboratoire a démontré que l'irradiation de la glande mammaire favorise la métastase de tumeurs recourants suite au recrutement de cellules CD11b+ dans la tumeur primaire et dans les poumons pré-métastatiques. Dans notre étude nous avons constaté que les cellules CD11b+ peuvent également jouer un rôle important dans la formation de métastases induites par la chimiothérapie ainsi que dans le maintien de la dormance in vivo. Nous avons également observé un enrichissement de cellules tumorales exprimant le marqueur de cellule souche Sca-1 parmi les cellules tumorales résistantes à la chimiothérapie et dans les cellules qui on formé des métastases in vivo. Des cellules CD11b+ dérivées du microenvironnement tumorale favorisent l'expansion de la population de cellules tumorales Sca-1+ in vitro. Ces résultats suggèrent que l'expansion d'une population de cellules tumorales avec des caractéristiques de cellules souches pourrait constituer un mécanisme par lequel la chimiothérapie induit des métastases dans des tumeurs récurrentes. D'autre part le même traitement de chimiothérapie peut générer des cellules résistantes avec un phénotype dormant. Les expériences in vivo indiquent que les cellules tumorales dormantes induisent une réponse immunitaire inflammatoire dans le ganglion lymphatique de drainage, qui est normalement réprimée par des cellules myéloïdes suppressives de tumeur (MDSC). Une analyse d'expression de gènes a révélé l'enrichissement de gènes liés à l'invasion et à la métastase dans les cellules tumorales récurrentes et des gènes liés à la réponse immunitaire dans les cellules tumorales dormantes. Les cellules CD11b+ issues du microenvironnement des tumeurs récurrents ont incité la croissance des cellules tumorales dormantes in vivo, tandis que les cellules CD11b+ dérivées de la rate de souris non porteuses de tumeur ne l'étaient pas. Les mécanismes moléculaires sous-jacents restent à découvrir. En conclusion, les résultats obtenus dans ce modèle indiquent que la chimiothérapie pourrait favoriser non seulement l'induction d'une dormance cellulaire, mais également que les cellules dormantes seraient adroits de induire une réponse immunitaire capable les maintenir dans un état de dormance prolongé. Un déséquilibre dans cette réponse immunitaire pourrait des lors briser cet état de dormance et induire une progression tumorale. Comprendre les mécanismes responsables de ces effets, en particulier l'identification des déterminants génétiques ou épigénétiques liés à la dormance vs la rechute, pourraient ouvrir la voie à des nouvelles thérapies visant le maintien d'un état de dormance permanente des cellules résiduelles après chimiothérapie.

Stomach content analyses of Simulium perflavum Roubaud 1906 (Diptera: Simuliidae) larvae from streams in Central Amazônia, Brazil

Stomach contents of Simulium perflavum Roubaud larvae were analyzed and compared with plankton and periphyton collected in five streams, in Central Amazonia (Manaus and Presidente Figueiredo counties), in Sep./Oct.1996 (dry season) and Feb./Mar. 1997 (rainy season). A total of 1,400 last-instar larvae were dissected; the stomach contents were analyzed using different methods: fresh and after oxidation. A total of 87 taxa (algae, diatoms and rotifers) were found in the stomach contents. In each stream, qualitative samples of plankton and periphyton were collected; these were mounted between slides and cover slips. A total of 94 taxa of plankton and 54 taxa of periphyton were collected. One species of Rotifera was present in the stomach contents, plankton and periphyton. Cluster analysis based on species composition of the organisms present in the stomach contents grouped the streams into two major groups, each belonging to a different drainage area. Correlations based on presence/absence of species of microalgae in the stomach contents, plankton and periphyton indicated significant associations (p<0.05) between stomach contents and plankton and between plankton and periphyton (z test); the Sorensen coefficient and cluster analysis corroborate the same associations.

Effect of irrigation water and processing on the microbial quality of lettuces produced and sold on markets in Dakar (Senegal)

The aim of this survey is to assess the microbiological impact of irrigation water on lettuces produced on two urban agricultural sites and sold on markets; 6 and 7%, respectively, of lettuces coming from the sites of Pikine and Patte d'Oie were Salmonella spp. positive. Lettuces irrigated with shallow groundwater (''Ceanes'' water) were more contaminated (8% at both Pikine and Patte d'Oie sites) compared to those irrigated with wastewater (4% at Pikine) or well water (5% at Patte d'Oie). As for the lettuces in marketplaces, their contamination seems to depend on the type of treatment occurring before sale. Lettuces previously washed in the ``Ceanes'' were more contaminated than those rinsed with tap water at the marketplace. Salmonella spp. have been isolated from all marketplaces. However, the rates of contamination in markets surrounding Patte d'Oie are higher (9 and 11% at Grand Yoff and Dalifort) than those surrounding Pikine (4 and 2% at Zinc and Sham) or Rufisque, the control (2%). Our results confirm that the reuse of wastewater in irrigation is an alternative to animal manure. Its risk of microbial contamination can be significantly reduced by washing the vegetables with tap water before they are sold. Copyright (C) 2010 John Wiley & Sons, Ltd.

Retinal fluorescein contrast arrival time of young patients with the hepatosplenic form of the Schistosomiasis mansoni

Schistosoma mansoni is responsible for lesions that can alter the hemodinamic of the portal venous circulation, lung arterial and venous sistemic systems. Therefore, hemodinamic changes in the ocular circulation of mansonic schistosomotic patients with portal hypertension and hepatofugal venous blood flow is also probable. The purpose of this study was to determine the fluorescein contrast arrival time at the retina of young patients with the hepatosplenic form of schistosomiasis, clinically and surgically treated. The control group included 36 non schistosomotic patients, mean age of 17.3 years, and the case group was represented by 25 schistosomotic patients, mean age of 18.2 years, who were cared for at The University Hospital (Federal University of Pernambuco, Brazil), from 1990 to 2001. They underwent digital angiofluoresceinography and were evaluated for the contrast arrival time at the early retinal venous phase of the exam. Both groups were ophthalmologically examined at the same hospital (Altino Ventura Foundation, Recife, Brazil), using the same technique. There was retardation of the retinal contrast arrival time equal or more than 70 sec in the eyes of three schistosomotic patients (12%) and in none of the control group, however, the mean contrast arrival time between the two groups were not statistically different. These findings lend support to the hypothesis that there could be a delay of the eye venous blood flow drainage.

Phenotypic divergence but not genetic distance predicts assortative mating among species of a cichlid fish radiation.

The hypothesis of ecological divergence giving rise to premating isolation in the face of gene flow is controversial. However, this may be an important mechanism to explain the rapid multiplication of species during adaptive radiation following the colonization of a new environment when geographical barriers to gene flow are largely absent but underutilized niche space is abundant. Using cichlid fish, we tested the prediction of ecological speciation that the strength of premating isolation among species is predicted by phenotypic rather than genetic distance. We conducted mate choice experiments between three closely related, sympatric species of a recent radiation in Lake Mweru (Zambia/DRC) that differ in habitat use and phenotype, and a distantly related population from Lake Bangweulu that resembles one of the species in Lake Mweru. We found significant assortative mating among all closely related, sympatric species that differed phenotypically, but none between the distantly related allopatric populations of more similar phenotype. Phenotypic distance between species was a good predictor of the strength of premating isolation, suggesting that assortative mating can evolve rapidly in association with ecological divergence during adaptive radiation. Our data also reveals that distantly related allopatric populations that have not diverged phenotypically, may hybridize when coming into secondary contact, e.g. upon river capture because of diversion of drainage systems.

Pathoecology of Chiribaya parasitism

The excavations of Chiribaya culture sites in the Osmore drainage of southern Peru focused on the recovery of information about prehistoric disease, including parasitism. The archaeologists excavated human, dog, guinea pig, and llama mummies. These mummies were analyzed for internal and external parasites. The results of the analysis and reconstruction of prehistoric life from the excavations allows us to interpret the pathoecology of the Chiribaya culture.

A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application.

The biocompatibility of a viscous, hydrophobic, bioerodible poly(ortho ester) (POE) intended for intraocular application was investigated. POE was evaluated as a blank carrier and as containing modulators of degradation. Each formulation was injected intracamerally and intravitreally in rabbit eyes, and clinical and histological examinations were performed postoperatively for 2 weeks. In the case of intracameral injections, polymer biocompatibility appeared to depend on the amount injected in the anterior chamber. When 50 microL was administered, the polymer degraded within 2 weeks, and clinical observations showed good biocompatibility of POE with no toxicity to the ocular tissues or increase in intraocular pressure. The injection of a larger volume, 100 microL, of POE, appeared inappropriate because of direct contact of polymeric material with the corneal endothelium, and triggered reversible edema and inflammation in the anterior chamber of the eye that regressed after a few days. After intravitreal administration, POE was well tolerated and no inflammatory reaction developed during the observation period. The polymer degraded slowly, appearing as a round whitish bubble in the vitreous cavity. The presence of modulators of degradation both improved POE biocompatibility and prolonged polymer lifetime in the eye. POE appears to be a promising biomaterial for clinical intraocular application.

A simple way to decompress the left ventricle during venoarterial bypass

OBJECTIVE: The aim of this investigation was to improve the hemodynamics during venoarterial bypass by remote decompression of the left ventricle (LV). METHODS: Venoarterial bypass was established in 5 bovine experiments (69+/-10 kg) by the transjugular insertion of a self-expanding cannula (smartcanula) with return through a carotid artery. Cardiogenic shock was simulated with ventricular fibrillation induced by an external stimulator. Left ventricular decompression was achieved by switching to transfemoral drainage of the pulmonary artery (PA) with a long self-expanding cannula. RESULTS: Initial pump flow was 4.7+/-0.9 l/min and the aortic pressure accounted for 75+/-21 mmHg. After induction of ventricular fibrillation, the pump flow dropped after 11+/-8 min to 2.5+/-0.1 l/min. Transfemoral decompression increased the pump flow to 5.6+/-0.7 l/min, while the RV pressure decreased from 27+/-9 to 3+/-5 mmHg, the PA pressure decreased from 29+/-7 to 5+/-4 mmHg, the LV pressure decreased from 29+/-6 to 7+/-2 mmHg, and the aortic pressure increased from 31+/-3 to 47+/-11 mmHg. CONCLUSIONS: Remote drainage of the pulmonary artery during venoarterial bypass allows for effective decompression of the left ventricle and provides superior hemodynamics.