Heat Sink Effect on Tumor Ablation Characteristics as Observed in Monopolar Radiofrequency,Bipolar Radiofrequency,and Microwave,Using Ex Vivo Calf Liver Model

Thermal ablation of liver tumors near large blood vessels is affected by the cooling effect of blood flow, leading to incomplete ablation. Hence, we conducted a comparative investigation of heat sink effect in monopolar (MP) and bipolar (BP) radiofrequency ablation (RFA), and microwave (MW) ablation devices.With a perfused calf liver, the ablative performances (volume, mass, density, dimensions), with and without heat sink, were measured. Heat sink was present when the ablative tip of the probes were 8.0 mm close to a major hepatic vein and absent when >30 mm away. Temperatures (T1 and T2) on either side of the hepatic vein near the tip of the probes, heating probe temperature (T3), outlet perfusate temperature (T4), and ablation time were monitored.With or without heat sink, BP radiofrequency ablated a larger volume and mass, compared with MP RFA or MW ablation, with latter device producing the highest density of tissue ablated. MW ablation produced an ellipsoidal shape while radiofrequency devices produced spheres.Percentage heat sink effect in Bipolar radiofrequency : Mono-polar radiofrequency : Microwave was (Volume) 33:41:22; (mass) 23:56:34; (density) 9.0:26:18; and (relative elipscity) 5.8:12.9:1.3, indicating that BP and MW devices were less affected.Percentage heat sink effect on time (minutes) to reach maximum temperature (W) = 13.28:9.2:29.8; time at maximum temperature (X) is 87:66:16.66; temperature difference (Y) between the thermal probes (T3) and the temperature (T1 + T2)/2 on either side of the hepatic vessel was 100:87:20; and temperature difference between the (T1 + T2)/2 and temperature of outlet circulating solution (T4), Z was 20.33:30.23:37.5.MW and BP radiofrequencies were less affected by heat sink while MP RFA was the most affected. With a single ablation, BP radiofrequency ablated a larger volume and mass regardless of heat sink.     

Regression of lymphomatous skin deposits in a chronic lymphocytic leukemia patient treated with the Toll-like receptor-7/8 agonist, imiquimod.

The identification of clinically relevant, active immunomodulatory agents is important for developing immunotherapeutic approaches to chronic lymphocytic leukemia (CLL) and other B-cell lymphomas that are not curable with conventional chemotherapy. In this investigation, the imidazoquinoline Toll-like receptor (TLR)-7/8 agonist, imiquimod, was found to mediate the clearance of a lymphomatous skin lesion in a CLL patient. Imidazoquinolines also activated TLR-7/8 signaling pathways, resulting in increased expression of costimulatory molecules on circulating tumor cells. These observations extend the therapeutic spectrum of imiquimod to cutaneous B-cell lymphomas and suggest the use of TLR-7/8 agonists in CLL immunotherapy.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Adverse outcomes of planned and unplanned pregnancies among users of natural family planning: a prospective study.

OBJECTIVES: The purpose of this study was to determine prospectively whether unplanned pregnancies are associated with adverse pregnancy outcomes among users of natural family planning. METHODS: Women who became pregnant while using natural family planning were identified in five centers worldwide: there were 373 unplanned and 367 planned pregnancies in this cohort. The subjects were followed up at 16 and 32 weeks' gestation and after delivery. The risks of spontaneous abortion, low birth-weight, and preterm birth were estimated after adjustment by logistic regression. RESULTS: The women with unplanned pregnancies were more likely to be at the extremes of age, to report more medical problems before and during the index pregnancy, and to seek antenatal care later in gestation than the women with planned pregnancies. However, women with planned pregnancies reported a higher rate of spontaneous abortion in previous pregnancies (28.8%) than did women with unplanned pregnancies (12.9%). There were no significant differences in the rates of spontaneous abortion, low birthweight, or preterm birth between the two groups. CONCLUSIONS: No increased risk of adverse pregnancy outcomes was observed among women who experienced an unplanned pregnancy while using natural family planning.     

Review of imaging techniques for the diagnosis of breast cancer: a new role of prone scintimammography using technetium-99m sestamibi

Imaging techniques currently used for the diagnosis of breast cancer are reviewed and compared. Besides mammography, magnetic resonance imaging, positron emission tomography, and thallium-201 scintimammography, a new role of technetium-99m sestamibi scintimammography is discussed. It is concluded that while mammography remains the procedure of choice in screening asymptomatic women for breast cancer, other imaging methods play an important role in detecting malignancies in symptomatic patients.^99mTc-sestamibi scintimammography has high sensitivity and improves the specificity of conventional mammography for the detection of breast cancer; with this technique, prone imaging is preferable to supine imaging.^99mTc-sestamibi scintimammography thus deserves further study as a screening technique.     

Pregnancy outcome associated with natural family planning (NFP): scientific basis and experimental design for an international cohort study

Although natural family planning (NFP) is a form of contraception without ostensible maternal risks (other than pregnancy), potential fetal risks could exist if aging gametes are involved in inadvertent fertilization. In the following report, we first review animal studies firmly establishing that aging sperm and aging oocytes (delayed fertilization) cause chromosomal abnormalities in mammals and other species. We next review human studies associating decreased coital frequency with trisomy and studies of NFP populations that generally show no increased frequency of anomalous offspring or spontaneous abortions. Our rationale for initiating an international cohort study is presented, along with the experimental design selected. Preliminary findings indicate that the experimental design chosen will indeed provide information allowing NFP safety to be assessed definitively.

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Resumen Aunque la planificación familiar natural (PFN) es una forma de anticoncepción sin riesgos maternos ostensibles, (fuera del embarzo) podrían existir posibles riesgos fetales di gametos que están envejeciendo son inadvertidamente fertilizados. La primera revisión de estudios en animales establece firmemente que espermatozoides y oocytos en envejecimiento (fertilización tardía), causan anormalidades cromosómicas en mamíferos y otras especies. A continuación revisamos estudios en humanos que asocian la disminución de la frecuencia coital con trisomía, y estudios de poblaciones practicando PFN que generalmente no muestran aumento en la frecuencia de descendientes anormales o de abortos espontáneos. Presentamos nuestras razones para iniciar el estudio de una cohorte internactional ademas del diseño experimental elegido proveerá información alegando que la inocuidad de la PFN sea definitivamente valorada.

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Resumé Bien que le planning familial naturel (PFN-NFP) soit une forme de contraception ne présentant pas de risques manifestes pour la mère (autres qu'une grossesse), il pourrait y avoir des risques potentiels pour le foetus si des gamètes âgés sont par inadvertance fécondés. Nous passons en revue tout d'abord des études effectuées sur des animaux, établissant fermement que le sperme veillissant et les oocytes vieillissants (fécondation retardée) provoquent des anomalies chromosomales chez les mammifères et d'autres espèces. Nous examinons ensuite des études sur des humains, qui associent diminution coitale et trisomie, et des études de populations pratiquant le PFN, qui ne révèlent généralement pas de fréquence accrue d'enfants anormaux ou d'avortements spontanés. Cette communication expose la raison pour laquelle nous avons entrepris une étude sur une cohorte internationale, ainsi que le concept d'expérimentation que nous avons choisi. Les constatations préliminaires indiquent que ce concept fournira véritablement des informations qui permettront d'évaluer de façon définitive la sécurité du PFN.

     

Evaluation of Port-A-Cul transport system for protection of anaerobic bacteria.

The protection of anaerobes in Port-A-Cul (PAC) transport system (Bioquest, Div. of Becton, Dickinson &Co., Cockeysville, Md.) tubes and vials was studied. Ten species of obligately anaerobic bacteria commonly isolated from clinical specimens were used to prepare simulated swab and fluid specimens in high and low concentrations. Samples in PAC tubes and vials were held for 2, 24, and 48 h at ambient temperature and in a refrigerator. In addition, samples of the simulated specimens were exposed to controlled anaerobic and aerobic conditions in vented tubes and vials, with and without PAC medium, at ambient and refrigerator temperatures. Viable bacterial colony counts from specimens in PAC tubes and vials used as recommended by the manufacturer were consistently greater than those from specimens exposed to the different controlled conditions. The protection in PAC was about equal for specimens with either high or low concentrations of bacteria. Protection of the anaerobes in PAC was more obvious with swab than with fluid specimens. Quantitative recovery of anaerobes from refrigerated PAC samples, with few exceptions, was comparable to that from PAC samples held at ambient temperature.     

Coxsackievirus B3-Induced Myocarditis : Perforin Exacerbates Disease, But Plays No Detectable Role in Virus Clearance

Viral myocarditis is remarkably common, being detected in approximately 1% of unselected asymptomatic individuals. Many cases are attributable to enteroviral infection, and in particular to coxsackievirus B3. The underlying pathogenesis is controversial, but most studies admit the important immunopathological role of infiltrating CD8⁺ (cytotoxic) T lymphocytes (CTLs). We have previously shown that CTLs play conflicting roles in coxsackievirus B (CVB) myocarditis; they assist in controlling virus replication, but also are instrumental in causing the extensive inflammatory disease, which often results in severe myocardial scarring. A role for perforin, the major CTL cytolytic protein, in CVB myocarditis has been suggested, but never proven. In the present study we use perforin knockout (PKO) mice to show that perforin plays a major role in CVB infection; in broad terms, perforin is important in immunopathology, but not in CVB clearance. For example, PKO mice are better able to withstand a normally lethal dose of CVB (100% survival of PKO mice compared with 90% death in +/+ littermates). In addition, PKO mice given a nonlethal dose of CVB develop only a mild myocarditis, whereas their perforin⁺ littermates have extensive myocardial lesions. The myocarditis in PKO mice resolves more quickly, and these mice show minimal histological sequelae; in contrast, late in disease the perforin⁺ mice develop severe myocardial fibrosis. PKO mice, despite lacking this major CTL effector function, can control the infection and eradicate the virus; growth kinetics and peak CVB titers are indistinguishable in PKO and perforin⁺ mice. Therefore, the immunopathological and antiviral effects of CTLs can be uncoupled by ablation of perforin; this offers a promising target for therapy of myocarditis. Furthermore, we evaluate the possible roles of apoptosis, and of chemokine expression, in CVB infection. In perforin⁺ mice, apoptotic cells are detected within the inflammatory infiltrate, whereas in their PKO counterparts, apoptotic myocyte nuclei are seen. Chemokine expression in both PKO and perforin⁺ mice precedes and parallels the course of myocarditis. Several chemokines are detectable earlier in PKO mice than in perforin⁺ mice, but PKO mice show reduced peak levels, and chemokine expression decays sooner. In particular, MIP-1α expression is barely detectable at any time point in PKO mice, but it is readily identified in perforin⁺ animals, peaking just before the time of maximal myocarditis; this is particularly interesting, given that MIP-1α knockout mice are resistant to CVB myocarditis, but remain able to control viral infection. Thus, the chemokine pathway offers a second route of intervention to diminish myocarditis and its sequelae, while permitting the host to eradicate the virus.