Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Antigens of Mycobacterium tuberculosis Recognized by Antibodies during Incipient, Subclinical Tuberculosis

Serum samples obtained from human immunodeficiency virus (HIV)-infected tuberculosis (TB) patients months prior to clinical TB were used to delineate the profile of Mycobacterium tuberculosis culture filtrate proteins recognized during subclinical TB. A subset of ~12 antigens was recognized by antibodies in these serum samples. Antibodies to two of these antigens (81 [88]-kDa malate synthase [GlcB] and MPT51) were present in serum samples obtained during incipient subclinical TB in 19 (~90%) of the 21 HIV-infected TB patients tested. These antigens will be useful for devising diagnostic tests that can identify HIV-positive individuals who are at a high risk for developing clinical TB.     

Second trimester abortion with ethacridine lactate plus Carboprost—which is the best time to administer the Carboprost?

Extra-amniotic ethacridine lactate plus intramuscular prostaglandin has become a popular method for terminating second trimester pregnancies. In this study, intrauterine pressure was continuously monitored in order to objectively compare the efficacy of 3 different times of administration of Carboprost (15-methyl PGF_2alpha)-at 2 hours, 4 hours and 8 hours after the instillation of ethacridine lactate. The best results were obtained with the administration of Carboprost 8 hours after the instillation of the extra-amniotic ethacridine lactate. The synergistic effect of ethacridine lactate and Carboprost is optimal after this time. This is probably because the ethacridine lactate will have produced sufficient cervical ripening to ensure optimal efficacy of the prostaglandin-induced uterine contractions in expelling the products of conception.

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Resumen Un método popular para terminar un embarazo en el segundo trimestre es el lactato de etacridina extraamniótico más prostaglandina intramuscular. En este estudio la presión intrauterina estuvo registrada continuamente a fin de comparar objetivamente la eficacia a 3 horarios diferentes de administración de Carboprost (15-metilo PGF_2alpha) a las 2 horas, 4 horas y 8 horas después de la instilación de lactato de etacridina. Los mejores resultados fueron obtenidos con la administración de Carboprost 8 horas después de la instilación extraamniótica de lactato de etacridina. Después de este tiempo el efecto sinergístico del lactato de etacridina y Carboprost es óptimo. Probablemente esto se debe a que el lactato de etacridina ha producido ablandamiento cervical suficiente para asegurar la óptima eficacia de las contracciones uterinas inducidas por la prostaglandina para eliminar los productos de la concepción.

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Résumé L'administration associée de lactate d'éthacridine extra-amniotique et de prostaglandine intramusculaire est devenue une méthode courante d'interruption de grossesses au deuxième trimestre. Au cours de cette étude, la pression intra-utérine a été contrôlée en continu afin de pouvoir comparer objectivement l'efficacité à trois moments différents d'administration de Carboprost (15-méthyle PGF_2alpha): 2 heures, 4 heures et 8 heures après l'instillation de lactate d'éthacridine. Les meilleurs résultats one été obtenus lorsque le Carboprost a été administré 8 heures après l'instillation de lactate d'éthacridine extra-amniotique. L'effet conjugué du lactate d'éthacridine et du Carboprost est optimal après ce délai, sans doute parce que le lactate d'éthacridine aura permis alors une maturation cervicale suffisante pour assurer une efficacité optimale aux contractions utérines provoquées par la prostaglandine en vue de l'expulsion des produits de conception.

     

Retinoblastoma. A clinical, immunohistochemical, and electron microscopic case report

A 4-year, 9-month-old boy had a history of leukocoria of the right eye for approximately six months prior to admission. The other eye was normal. There was no family history of retinoblastoma. Funduscopy disclosed a large white mass extending from the nasal pars plana to the mid-pupillary zone and the posterior pole with a near total retinal detachment in the superior temporal quadrant. A B-scan ultrasound showed an echo dense area of the anterior portion of the mass. A CT scan showed intraocular tissue densities with no evidence of optic nerve involvement or extraocular extension. Immunohistochemistry of a fresh frozen portion of tumor revealed reactivity with antibodies directed against interphotoreceptor retinoid-binding-protein (IRBP), neuron-specific enolase, glial fibrillary acidic protein, S-antigen, focal reactivity with opsin, and scattered cytoplasmic staining for cyclic GMP and cyclic GMP phosphodiesterase. Biochemical analysis of fresh frozen tissue samples confirmed the presence of IRBP. Transmission electron microscopy disclosed occasional Flexner-Wintersteiner rosettes connected by zonula adherens-like junctions. These showed inner segment-like structures containing prominent mitochondria, portions of cilia and fragments of outer segment material. These data, along with the immunocytochemistry indicates a predominant neuronal nature of the tumor cells with significant photoreceptor-like differentiation.     

Homogeneously staining region in anthracycline-resistant HL-60/AR cells not associated with MDR1 amplification.

Anthracycline-resistant HL-60/AR cells and their drug-sensitive HL-60/S counterparts were characterized by karyotypic analysis and examined for the overexpression of DNA and mRNA sequences coding for P-glycoprotein (Pgp). The HL-60/S cells were karyotypically stable over a 5-year period of study (1986-1991), except for an additional small Giemsa-positive band noted at 7q22 in cultures harvested in 1987, but not in 1986. This change did not affect drug sensitivity. The drug-resistant HL-60/AR cells examined in 1986, 1987, and 1991 demonstrated a very stable karyotype. The most striking feature was a large homogeneously staining region in the long arm of chromosome 7 (7q11.2), and translocation of the remainder of the long arm to another centromere. Other changes in the HL-60/AR cells included inversion in 9q, partial deletion of the short arm of chromosome 10p, addition of material to the p arm of der(16), loss of chromosome 22, and the appearance of a new marker chromosome. Both HL-60/S and the HL-60/AR cells were found not to amplify DNA or mRNA sequences coding for the Pgp. Thus, although the HL-60/AR cells possess the classical multidrug resistance phenotype and demonstrate a homogeneously staining region near the region of the MDR1 gene, their resistance is due to mechanisms other than those coded for by MDR1.     

Dengue fever presenting with acute colitis.

Gastrointestinal manifestations of dengue fever are mainly in the form of bleeding or liver function abnormalities. Dengue fever presenting as acute colitis-like picture is not reported to date. We report a 50-year-old man with dengue fever presenting with lower gastrointestinal bleeding and colonoscopic features of acute inflammatory colitis.     

Studies on capsaicin inhibition of chemically induced lipid peroxidation in the lung and liver tissues of rat

Previous work from this laboratory has already indicated that capsaicin, stabilizes the rat lung membrane lipid system on long-term treatment. This stabilization of the membrane is further supported by our present findings that capsaicin pretreatment causes significant inhibition of various chemically induced lipid peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes induced by different chemical irritants such as chloroform, dichloromethane, carbon tetrachloride as well as ferrous sulphate.     

Susceptibility of hamsters to caecal amoebiasis by oral infection

A method is described for successfully establishing caecal amoebiasis in hamsters which were not fed and which were pretreated with 1 ml of magnesium sulphate every 24 hours for three days and then given 12 x 10(5) trophozoites of the HM-1 axenic strain or 18 x 10(5) trophozoites of the HK-9 axenic strain of Entamoeba histolytica by the oral route. All the animals developed diarrhoea within 24 hours of infection. When the animals were killed on the fifth day after infection the caecum was swollen and fused. Large macroscopic ulcers full of pus could be seen in the caecum. None of the control animals showed any of the changes mentioned above.