CT of calcified liver metastases in colorectal carcinoma

PURPOSE: To assess the incidence, characteristics and prognostic significance of calcification within colorectal hepatic metastases. MATERIALS AND METHODS: A retrospective analysis of CT in 265 patients with locally advanced or metastatic cancer was performed. Four groups were defined: (a) calcification within liver metastases prior to therapy, (b) noncalcified liver metastases with development of calcification on therapy, (c) noncalcified liver metastases, and (d) advanced local tumour without liver metastases. The number of calcified deposits in each patient was documented. A marker lesion was analysed for character, distribution and percentage of calcification. Survival between the four groups was compared. RESULTS: Twenty-nine (11%) patients had calcified liver metastases at presentation and 10 (4%) developed calcification during chemotherapy. Analysis of a marker lesion showed that the most frequent characteristic was fine calcification with a variable distribution. The most frequent change on treatment was alteration in the extent of calcification. Calcification developing on treatment was usually central. There was no difference in survival between groups 1, 2 and 3, but groups 1, 2 and 3 had a shorter survival than group 4. CONCLUSION: Calcification of liver metastases shows a variable pattern and may develop or change during therapy. Liver metastatic calcification may not carry any prognostic significance in colorectal cancer.     

HIV-associated brain pathology: a comparative international study

OBJECTIVES: This study examined the use of aides in occupational therapy practice, the supervision and training of aides, and practitioners' attitudes toward the use of aides. METHOD: A questionnaire was mailed to a systematically selected sample of 510 occupational therapists and occupational therapy assistants. The response rate was 74%. RESULTS: The use of occupational therapy aides is prevalent in a variety of settings. Forty percent of respondents reported that they currently work with aides, whereas 23% reported that they have never worked with aides. Occupational therapy aides perform a variety of tasks and receive various levels and amounts of supervision and training. Of those respondents who delegated specific skilled tasks to aides, 76% reported daily contact for purposes of supervision and training. Nineteen percent who currently work or have worked with aides reported being in a situation where an ethical issue arose related to aide use. CONCLUSION: On the basis of the data, it is suggested that occupational therapy practitioners would benefit from taking a proactive role in determining how aides can be used to maximize service delivery while maintaining quality services. There also appear to be ethical concerns related to appropriate delegation of tasks to aides and to their supervision and training.     

Population pharmacokinetics in veterinary medicine: potential use for therapeutic drug monitoring and prediction of tissue residues

Population pharmacokinetics can be defined as a study of the basic features of drug disposition in a population, accounting for the influence of diverse pathophysiological factors on pharmacokinetics, and explicitly estimating the magnitude of the interindividual and intraindividual variability. It is used to identify subpopulations of individuals that may present with differences in drug kinetics or in kinetic/dynamic responses. Rooted in procedures used in engineering systems, population pharmacokinetics methods were conceived as a means to determine the pharmacokinetic profile in populations in which a sparse number of samples were obtained per individual, such as those in late stage human clinical trials. This is the situation commonly encountered in all aspects of veterinary medicine. The exploratory nature of this technique allows one to probe relationships between clinical factors (such as age, gender, renal function, etc.) and drug disposition and/or effect. Similarly, the utilization of these techniques in the clinical research phases of drug development optimize the determination of efficacy and safety of drugs. Given the observational nature of most studies published so far, statistical methods to validate the population models are necessary. Simulation studies may be conducted to explore data collection designs that maximize information yield with a minimum expenditure of resources. The breadth of this approach has allowed population studies to be more commonly employed in all areas of drug therapy and clinical research. Finally, in veterinary medicine, there is an additional field in which population studies are potentially ideally suited: the application of this methodology to the study of tissue drug depletion and drug residues in production animals, and the establishment of withdrawal times tailored to the clinical or production conditions of populations or individuals. Such application would provide a major step toward assuring a safe food supply under a wide variety of dose and off-label clinical uses. Population pharmacokinetics is an ideal method for generating data in support of the implementation of flexible labelling policies and extralabel drug use recently approved under AMDUCA (Animal Medicinal Drug Use Clarification Act. 21 CFR Part 530).     

Ischemic myelomalacia associated with fibrocartilaginous embolism in multiple finishing swine

Latin America generates a low proportion of the references quoted in Medline, the most popular health-related literature search database in the world. This paper explores references from and about Colombia in Medline during the period 1987-1996. Topics addressed, patterns of authorship and research locations are established. The number of Latin American journals indexed in Medline has been progressively reduced during this 10-year period, with Colombian journals completely excluded since 1991. During this 10-year period, the total output of Colombian research institutions in foreign journals consisted of 531 articles, 41% (219) of which come from the four leading universities. These figures are substantially lower than those from other countries of the region such as Venezuela or Chile. Despite some governmental efforts, Colombia continues to have a low scientific output and has yet to attract the interest of foreign researchers. Alternatives for development of Latin American research and publications are offered.     

Effects of amount and type of dietary fibre (soluble and insoluble) on short-term control of appetite

OBJECTIVE: The calcium (Ca) pump of cardiac sarcoplasmic reticulum (SR) membranes is vulnerable to oxidation and hence likely to be damaged by chlorinated compounds, specifically hypochlorite (NaOCl) and monochloramine (NH2Cl), the most potent oxidants produced upon neutrophil activation. This could occur during prolonged ischemia or myocardial infarction when tissue levels of catecholamines are high. Phospholamban (PLN), the phosphorylatable regulator of the Ca pump, plays a central role in the effects of beta-adrenergic agonists on the heart. The purpose of this study was to investigate a possible role of PLN in determining the pump's sensitivity to NaOCl and NH2Cl. METHODS: Ca-uptake and Ca(2+)-ATPase activities in purified phosphorylated and control canine cardiac microsomes, incubated at increasing concentrations of NaOCl or NH2Cl, were related to the extent of PLN phosphorylation by protein kinase A, which was quantitated by PhosphorImager analysis. RESULTS AND CONCLUSIONS: Our data indicate that microsomal phosphorylation protects the Ca pump fully against 10 microM NaOCl or NH2Cl, which inhibit Ca-uptake by 21-41% when assayed at 25 or 37 degrees C and saturating Ca2+ in unphosphorylated microsomes, and protects partially at higher oxidant concentrations. The protective effect of protein kinase A on Ca-uptake is proportional to the amount of phosphorylated PLN. No comparable protection against similar oxidative damage of the Ca pump is observed when light fast skeletal muscle microsomes, which lack PLN, are incubated under conditions favorable for phosphorylation nor when PLN's inhibition of the cardiac Ca pump is relieved by proteolytic cleavage of its cytoplasmic domain. Our findings contribute toward an understanding of possible endogenous protective mechanisms that may promote calcium homeostasis in myocardial cells in inflammatory states associated with neutrophil activation and may suggest an approach toward development of protective strategies against oxidative damage in the heart.     

Rainbow trout liver expresses two iodothyronine phenolic ring deiodinase pathways with the characteristics of mammalian types I and II 5'-deiodinases

Deiodinases are major determinants of thyroid hormone tissue availability and disposal. The knowledge of the expression of these enzymes in lower species is important to understand evolutionary and ontogenetic aspects of thyroid hormone action and metabolism. Here we have studied outer ring deiodination in the trout liver using both reverse T3 (rT3) and T4 as substrates. The use of rT3 disclosed two enzymatic components with the characteristics of mammalian types I and II 5'-deiodinases. The high rT3-K(m) type I 5'-deiodinase activity (180 nM) has a low cofactor requirement (5 mM dithiothreitol) and is relatively sensitive to propylthiouracil inhibition, whereas the low rT3-K(m) activity was akin to the outer ring deiodination of T4 in these regards. The use of T4 exhibited only a single type of activity with a low K(m) (0.63 nM), a relatively high cofactor requirement (25 mM dithiothreitol), and propylthiouracil-resistance. Teleosts constitute a unique example of type II activity expression in the liver of an adult vertebrate. Furthermore, the Vmax of this enzyme is as high as that found in comparable homogenates from hypothyroid mammalian tissues, whereas the Vmax of the type I activity is lower than that of mammalian liver. These findings are in consonance with the peculiar kinetics of T3 in trout liver, kinetics remarkably similar to those of the mammalian pituitary, cerebral cortex, and brown adipose tissue, which also preferentially express type II deiodinase.     

Combined assessment of myocardial perfusion and left ventricular function with exercise technetium-99m sestamibi gated single-photon emission computed tomography can differentiate between ischemic and nonischemic dilated cardiomyopathy

The purpose of this study was to determine whether exercise technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) accurately distinguishes between patients with ischemic cardiomyopathy and patients with nonischemic left ventricular systolic dysfunction. Noninvasive tests have previously failed to accurately separate patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Technetium-99m gated SPECT imaging offers advantages that have the potential to overcome the limitations of previous studies. Thirty-seven adults with a left ventricular ejection fraction < or = 35%, including 24 patients with nonischemic cardiomyopathy and 13 patients with ischemic cardiomyopathy, were prospectively evaluated using symptom-limited metabolic exercise treadmill testing with technetium-99m sestamibi gated SPECT imaging. Interpretation of myocardial perfusion and regional wall motion was performed, using a 17-segment model. Summed stress, rest, and reversibility perfusion defect scores were determined, and the variance of segmental wall motion scores was computed. Summed stress, rest, and reversibility perfusion defect scores were significantly lower in nonischemic cardiomyopathy patients, compared with those with ischemic cardiomyopathy (summed stress defect score: 6.9 +/- 3.8 vs 32.9 +/- 7.7, respectively, p <0.001). Variability in segmental wall motion was also significantly lower in patients with nonischemic cardiomyopathy compared with those with ischemic cardiomyopathy (variance: 0.3 +/- 0.3 vs 1.2 +/- 0.8, respectively, p <0.001). Thus, assessment of myocardial perfusion and regional ventricular function with exercise technetium-99m sestamibi gated SPECT imaging can reliably distinguish between patients with ischemic cardiomyopathy and patients with nonischemic dilated cardiomyopathy.     

Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).     

Regulation of insulin-stimulated GLUT4 translocation by Munc18c in 3T3L1 adipocytes

Insulin stimulates glucose transporter (GLUT) 4 vesicle translocation from intracellular storage sites to the plasma membrane in 3T3L1 adipocytes through a VAMP2- and syntaxin 4-dependent mechanism. We have observed that Munc18c, a mammalian homolog of the yeast syntaxin-binding protein n-Sec1p, competed for the binding of VAMP2 to syntaxin 4. Consistent with an inhibitory function for Munc18c, expression of Munc18c, but not the related Munc18b isoform, prevented the insulin stimulation of GLUT4 and IRAP/vp165 translocation to the plasma membrane without any significant effect on GLUT1 trafficking. As expected, overexpressed Munc18c was found to co-immunoprecipitate with syntaxin 4 in the basal state. However, these complexes were found to dissociate upon insulin stimulation. Furthermore, endogenous Munc18c was predominantly localized to the plasma membrane and its distribution was not altered by insulin stimulation. Although expression of enhanced green fluorescent protein-Munc18c primarily resulted in a dispersed cytosolic distribution, co-expression with syntaxin 4 resulted in increased localization to the plasma membrane. Together, these data suggest that Munc18c inhibits the docking/fusion of GLUT4-containing vesicles by blocking the binding of VAMP2 to syntaxin 4. Insulin relieves this inhibition by inducing the dissociation of Munc18c from syntaxin 4 and by sequestering Munc18c to an alternative plasma membrane binding site.