Search

ObjectiveTo document the efficacy of intratumoural injections of 5‐fluorouracil for the treatment of equine sarcoids.

Microfluidic hydrodynamic chromatography performed in serpentine microchannels etched on chips is analyzed in the limiting case of chips containing a large number of periodically arrayed turns. Comparison is made between these results and those for a straight channel of the same length as the curvilinear channel, all other things being equal. Explicitly, generalized Taylor−Aris dispersion (macrotransport) theory for spatially periodic systems is adapted to compute the chip-scale solute velocity Ū* and dispersivity &Dmacr;* for effectively point-size, physicochemically inert Brownian particles entrained in a low Reynolds number, pressure-driven solvent flow occurring within the curvilinear interstices of such serpentine devices. Attention is focused upon relatively thin channels of uniform cross section, enabling the various transport fields pertinent to the problem to be expressed as regular perturbation expansions with respect to a small dimensionless parameter ε, representing the ratio of channel half-width to curvilinear channel length per turn. The generic leading-order results obtained for Ū* and &Dmacr;*, valid for any sufficiently “thin” channel, formally demonstrate that the serpentine geometry results simply reproduce those for a straight channel, when account is taken of the channel's “tortuosity,” namely the square of the ratio of curvilinear serpentine length to rectilinear straight channel length&sbd;a conclusion shown to accord with intuition.

There is an evident need to measure the comprehensive burden of morbidity experienced by survivors of brain tumours in childhood. To this end, a questionnaire based on the Health Utilities Index mark 2 (HUI2) and mark 3 (HUI3) systems was completed independently for a cohort of such children by their parents, by a nurse, by physicians and by a selected group of the children themselves. Each of the HUI2 and HUI3 systems consists of a multi-attribute health status classification scheme linked to a preference function which provides utility scores for levels within single attributes (domains of health) and for global health states. All eligible families (n=44) participated. Even cognitively impaired children of at least 9.5 years of age could complete the questionnaire. The greatest burden of morbidity, occurring in two-thirds of children, was in the attribute of cognition. Surprisingly, almost one-third of children experienced pain. Global health status was lowest in children who underwent radiotherapy before the age of 5 years and the corresponding utility scores were related inversely to the volume irradiated. Children with demonstrable disease had lower scores than those in whom disease was not evident. There was a high level of agreement (intraclass correlation coefficients >0.5) on formal assessment of inter-rater reliability for global health-related quality of life utility scores. The usefulness of measures of health status and health-related quality of life, in children surviving brain tumours, has been demonstrated by this study.

Based on the encouraging findings in part I of our study, and on the relevant research literature, several sociodemographic factors were added to the causal sequence proposed by the distribution of consumption model and corroborated by a statistical technique known as the analysis of linear structural relations (LISREL). The sociodemographic factors were added in two alternative fashions. Although neither approach proved to be significantly superior, the basic causal sequence identified in part I was maintained, and the sociodemographic factors were found to be intimately involved in the process that leads to alcohol-related morbidity and alcohol-related mortality in the general population. The findings are discussed with reference to their implications for prevention via public policy.

The main objective of this study was to identify the number and type of alcoholism programs in the province of Ontario, Canada, which endorse treatment goals other than complete abstinence. A survey of all alcoholism programs in the province revealed that 36.7% of the programs found nonabstinence goals appropriate for at least some clients. Endorsement of nonabstinence goals was lowest for detoxication centers and residential treatment services, and highest for nonresidential programs and assessment-referral services. Endorsement of nonabstinence goals was higher among programs aimed at young people and those associated with the criminal justice system. Within a treatment program, the use of various kinds of assessment methods and treatment modalities did not appear to be closely associated with the endorsement of abstinence vs nonabstinence treatment goals.

One of the major approaches to alcoholism prevention is referred to as the distribution of consumption model. This prevention model can be summarized as a causal model whereby the availability of alcoholic beverages has a direct causal effect on the aggregate level of alcohol consumption in the population and, in turn, an indirect effect on the incidence and prevalence of alcohol-related damage. This article summarizes an application of a statistical technique known as the analysis of linear structural relations (LISREL) to a set of Ontario data concerning alcohol availability, alcohol consumption and alcohol-related damage. Results substantiated the existence of specific causal paths consistent with the model. Several procedures for assessing the overall goodness-of-fit of the model suggested that it adequately fit the data. The results provide reasonable statistical evidence that government policies restricting the retail availability of alcoholic beverages will reduce the per capita rates of alcohol consumption and, in turn, reduce the level of alcohol-related mortality and morbidity in the general population.

Recently, cyclooctylpyranone derivatives with m-carboxamide substituents (e.g. 2c) were identified as potent, nonpeptidic HIV protease inhibitors, but these compounds lacked significant antiviral activity in cell culture. Substitution of a sulfonamide group at the meta position, however, produces compounds with excellent HIV protease binding affinity and antiviral activity. Guided by an iterative structure-based drug design process, we have prepared and evaluated a number of these derivatives, which are readily available via a seven-step synthesis. A few of the most potent compounds were further evaluated for such characteristics as pharmacokinetics and toxicity in rats and dogs. From this work, the p-cyanophenyl sulfonamide derivative 35k emerged as a promising inhibitor, was selected for further development, and entered phase I clinical trials.

Antigen receptor-stimulated cell death of developing, immature T cells plays an important role in shaping the repertoire of antigens to which mature T cells will respond, but a role for receptor-stimulated death in controlling responses of mature T cells is controversial. Mutant lpr/lpr mice exhibit an autoimmune syndrome similar to systemic lupus erythematosus. Here we demonstrate that these mice have a defect in antigen-stimulated suicide of activated T cells in mature CD4+ and CD8+ T cell compartments. The defective suicide pathway is evident when the T cells are stimulated with antigen on antigen-presenting cells or with immobilized anti-CD3 in the absence of antigen-presenting cells. These studies, in concert with the work of others, suggest that antigen-stimulated death of mature cells may be important both in establishing peripheral tolerance and in limiting inflammation during normal immune responses.

Subcutaneous clonidine (0.01--1.0 mg/kg) was found to delay small intestinal transit but not gastric emptying in the unanesthetized rat, with a maximal effect seen at 0.1 mg/kg. Gastric emptying was expressed as the percentage of intragastrically administered 51Cr emptied into the small intestine after 45 min. Small intestinal transit was the percentage of the small intestinal length traveled 45 min after oral or duodenal administration of black ink. The depression of small intestinal transit by clonidine to 20 to 30% of control values was blocked by phentolamine and yohimbine, but not by prazosin or phenoxybenzamine, suggesting a presynaptic (alpha-2) agonist action of clonidine. Pretreatment of rats with 6-hydroxydopamine, propranolol, atropine, methysergide, naloxone, mepyramine or metiamide failed to alter the effects of clonidine. These results suggest that an alpha adrenergic receptor, possibly presynaptic, regulates small bowel propulsion in rat without involvement of acetylcholine, norepinephrine, endorphins, histamine or serotonin.

Summary: 16,16-Dimethyl PGE2 (dmPGE2) has previously been shown to protect the in vivo rat liver against CCl4-induced damage. These studies were undertaken to determine if this protection could be demonstrated in vitro where factors of absorption, secretion, and blood flow are not present. Primary hepatocyte cultures were established by perfusing rat liver with collagenase. Hepatocytes were plated at a density of 2104 cells/cm, allowed 90 min to attach, then stabilized in L15 medium for 18 h. Hepatocytes were then challenged with CCl4 with concomitant exposure to 10−9 to 10−5 M dmPGE2, stearic acid, oleic acid, or ethanol vehicle (0.00001 to 0.1%). After 1 h, challenge was aspirated and cells were stained with 0.04% trypan blue to determine viability. Hepatocytes in the vehicle groups took up more trypan when exposed to CCl4 than those treated with dmPGE2, stearic acid, or oleic acid at concentrations of 10−9 to 10−7 M. At 0.1% ethanol vehicle protected as well as all other treatments. Protection against CCl4 by dmPGE2, stearic, and oleic acids as well as high concentrations of ethanol may occur by altering the metabolism of CCl4.

Recent studies by Crowel1 and Smith1 and Rush et al2 have drawn attention to the significance of the oxygen deficit incurred during hemorrhagic shock. The results of these investigations support the concept of progressive stagnant hypoxia as the final pathway of irreversible hemorrhagic shock.3 Endotoxin shock is thought to produce death in a similar fashion, ie, vasoactive substances are released which lead to venous pooling, decreased venous return, decreased cardiac output, and poor tissue perfusion. The latter results in stagnant hypoxia with eventual cellular death.The following experiments were undertaken to quantitate the hypoxia sustained during lethal endotoxin shock by measuring oxygen deficit and lactate production following the administration of Escherichia coli endotoxin. The data reported in this paper were derived from animals that did not develop a pyrogenic response to the endotoxin. If shock was accompanied by fever, oxygen consumption rose, despite progressive deterioration terminating in

Current methods for the visualization of blood cells, although ranging in power of resolution from optical to ultrastrucutral level, are limited to a two-dimensional presentation. Much important information has been gained by use of these techniques, but many points of controversy remain. This study described the surface morphology of erythrocytes, leucocytes and platelets in circulating blood and bone marrow as visualized by the scanning electron microscope. Bone marrow aspirate and sequestrenated whole blood were fixed in phosphate-buffered 0.5% glutaraldehyde (pH 7.3) at 4° for 3 nr. After washing in distilled water, thin films of the cells and fragments were deposited and dried on glass slides. The slides were trimmed to a size suitable for attachment to the aluminium specimen stub and after attachment were covered with a layer of gold and examined in the scanning electron microscope. Alternative methods of fixation were undertaken, and in some instances the films were stained with Romanowsky stains or toluidine blue after glutaraldehyde fixation or smeared on glass slides initially and stained with similar stains before glutaraldehyde fixation.

The definition and classification of the sideroblastic anaemias was discussed. Clinical and laboratory details of three patients were given, each patient representing one aspect of these anaemias. The first patient passed from a phase of refractory anaemia with bone marrow sideroblastosis to frank acute leukaemia. The second patient's sideroblastic anaemia was associated with lead poisoning from an unusual source. The third patient's sideroblastic anaemia was responsive to pyridoxine. Possible abnormalities in haem synthesis leading to marrow sideroblast formation were mentioned, but it was concluded that insufficient evidence was yet available to justify any firm statement concerning the pathogenesis of the sideroblastic anaemias.