Developmental stages in experimental liver metastases: relation to invasiveness

We have previously reported that an invasive morphotype can be evoked in a rat colon carcinoma by transplanting it into pre-induced subcutaneous granulation tissue. We have now studied the interaction of the same tumor with liver tissue, which is extremely poor in connective tissue in comparison with the subcutaneous site. Tumor cells were injected into the portal system and the resulting experimental liver metastases were examined by electron microscopy and immunohistochemistry. Early metastases consisted of well-differentiated acini, fully surrounded by connective tissue that was derived from the periportal stroma. In a later stage, this connective tissue was overgrown by tumor cells and, almost immediately, acinar differentiation was lost. Most metastases eventually reached the liver capsule, which reacted by forming a layer of granulation tissue. Only in this layer, we observed invasion by thin tumor cell strands, which were often intimately associated with fibroblasts or with blood capillaries. The tumor cells remained smooth and rounded during this process. After fully penetrating the granulation tissue, the tumor cell strands reached the liver surface, where they formed poorly structured papillary masses that were nearly devoid of stroma. Our observations indicate that, even in a relatively homogeneous organ like the liver, the tumor-host interaction is highly complex and dynamic. They also confirm the notion that granulation tissue stimulates tumor invasiveness. Finally, they show that tumor cells can actively invade host tissues without exhibiting a "fibroblastic" morphology.     

Occupational factors and renal disease

The male-to-female ratio of patients requiring dialysis treatment commonly approaches 2:1. It is proposed that environmental factors, particularly occupational exposure to hydrocarbons, may account for the excess number of male patients. The term "hydrocarbon" refers to the aliphatic, alicyclic, aromatic, and halogenated hydrocarbons (carbon tetrachloride, chloroform); glycols (ethylene glycol, diethylene glycol, dioxane, glycerol); and organic solvents. Hydrocarbons commonly find use as solvents in industrial manufacturing practices because of their lipid solubility. Hydrocarbons have long been known to be neurotoxicants, affecting both peripheral and central nervous systems. Although benzene and its derivative have a known association with uroepithelial tumors, there is now a considerable body of evidence suggesting a possible role for hydrocarbon exposure in the development of non-neoplastic renal diseases. This article presents an epidemiological case for such an association and critically reviews the literature.     

Kinetic study of the aqueous electropolymerization of acrylamide,acrylonitrile andN,N′-methylene-bisacrylamide on an aluminium alloy cathode

This study concerns the potassium persulphate electroinitiated polymerization of acrylamide, acrylonitrile andN, N-methylene-bisacrylamide on a 5182 aluminium-magnesium alloy. Kinetic studies of the polymerization gave the polymerization as -d[M]/dt=K(CD)^0.99 [Persulphate]^1.12 [M]^2.33, whereCD is current density (mA cm^–2), [M] is monomer concentration (mol cm^–3),K is a constant andt is time (s). It is proposed that the thick swollen polymer coating restricted the diffusion of monomers and initiators to the electrode. The problem of mass transfer by diffusion in the present system was confirmed by measurements of the diffusion coefficient and by electron transfer fraction experiments carried out through the use of a cyclic voltammetry technique.     

"En-bloc" vertebrectomy in the mobile lumbar spine

BACKGROUND: Primary tumors of the vertebral bodies have previously been treated with total or subtotal excision in a piecemeal fashion (intralesional excision). Radiation therapy has been used to help control tumor growth. Recurrence rates with an intralesional, piecemeal removal of vertebral tumors have been unacceptably high. This study describes a method to excise a lumbar vertebra "en-bloc," and in the process, to perform a marginal (extralesional) resection of a primary tumor of the mobile lumbar spine that allows for a potential surgical cure. METHODS: A combined posterior-anterior procedure allows for an extralesional, marginal resection of the tumor and the involved vertebra. All posterior bony elements, including the pedicles and the adjacent intervertebral discs, are removed via a posterior approach. An anterior, retroperitoneal approach is then used to remove the vertebral body/tumor as a single specimen. The nerve roots at the involved levels are spared and the spine is instrumented and fused both posteriorly and anteriorly. RESULTS: Three patients successfully had combined posterior-anterior resections of lumbar vertebral chordomas. No permanent neurological complications occurred. Overall morbidity of the procedure was acceptable. At 31-month follow-up, no tumor recurrence has been detected. CONCLUSIONS: "En-bloc" resection of a primary vertebral tumor of the lumbar spine is technically demanding, but potentially curative. The alternative approaches-intralesional excision, radiation therapy, or a combination-are unable to cure these tumors. Long-term, 10-year follow-up will be necessary to confirm whether this en-bloc approach provides a surgical cure.     

Leonardo da Vinci: the search for the soul

The human race has always contemplated the question of the anatomical location of the soul. During the Renaissance the controversy crystallized into those individuals who supported the heart ("cardiocentric soul") and others who supported the brain ("cephalocentric soul") as the abode for this elusive entity. Leonardo da Vinci (1452-1519) joined a long list of other explorers in the "search for the soul." The method he used to resolve this anatomical problem involved the accumulation of information from ancient and contemporary sources, careful notetaking, discussions with acknowledged experts, and his own personal search for the truth. Leonardo used a myriad of innovative methods acquired from his knowledge of painting, sculpture, and architecture to define more clearly the site of the "senso comune"--the soul. In this review the author examines the sources of this ancient question, the knowledge base tapped by Leonardo for his personal search for the soul, and the views of key individuals who followed him.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

Learning the higher-order structure of a natural sound

Unsupervised learning algorithms paying attention only to second-order statistics ignore the phase structure (higher-order statistics) of signals, which contains all the informative temporal and spatial coincidences which we think of as 'features'. Here we discuss how an Independent Component Analysis (ICA) algorithm may be used to elucidate the higher-order structure of natural signals, yielding their independent basis functions. This is illustrated with the ICA transform of the sound of a fingernail tapping musically on a tooth. The resulting independent basis functions look like the sounds themselves, having similar temporal envelopes and the same musical pitches. Thus they reflect both the phase and frequency information inherent in the data.     

Reinforcement Learning Rules in a Repeated Game

This paper examines the performance of simple reinforcement learningalgorithms in a stationary environment and in a repeated game where theenvironment evolves endogenously based on the actions of other agents. Sometypes of reinforcement learning rules can be extremely sensitive to smallchanges in the initial conditions, consequently, events early in a simulationcan affect the performance of the rule over a relatively long time horizon.However, when multiple adaptive agents interact, algorithms that performedpoorly in a stationary environment often converge rapidly to a stableaggregate behaviors despite the slow and erratic behavior of individuallearners. Algorithms that are robust in stationary environments can exhibitslow convergence in an evolving environment.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.