Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Transjugular intrahepatic portosystemic shunts (TIPS): effects of respiratory state and patient position on the measurement of Doppler velocities

OBJECTIVE: The purpose of this prospective study was to examine the effects of patient position and respiratory state on the measurements of Doppler velocities in transjugular intrahepatic portosystemic shunts. SUBJECTS AND METHODS: Thirty-eight transjugular intrahepatic portosystemic shunts in 34 consecutive patients were studied using Doppler sonography. Peak velocities were measured in the mid shunt with the patient in three positions (supine, sitting upright, and left lateral decubitus) and two respiratory states (deep inspiration and quiet respiration). A mixed linear regression model was used to assess statistically significant differences among the six velocity measurements. RESULTS: Peak velocities in the mid stent averaged 22 cm/sec greater in quiet respiration than in deep inspiration, which was a significant difference (p < 0.00001). Differences in velocities in the three patient positions were not significant (p = 0.53). Using 90-190 cm/sec as the normal range, the peak velocity shifted from normal to abnormal levels by changing respiratory state in 17 (45%) of 38 studies. Using 60 cm/sec as the lower normal limit, the peak velocity fell below the normal range with inspiration in 10 (26%) of 38 studies. In 12 (32%) of 38 studies, a decline in peak velocity exceeding 50 cm/sec could be induced by inspiration. CONCLUSION: Peak systolic velocity in transjugular intrahepatic portosystemic shunts is substantially altered by the respiratory state of the patient at the time of the measurement, but not by the patient position. Respiratory state must be taken into account in the interpretation of peak velocity for shunt stenosis.     

Preteen children and illegal drugs

In this paper we report the results of research on the nature and extent of legal and illegal drug use among preteens and those factors associated with illegal drug use at this young age. The paper is based upon a survey of 2318 ten to twelve year olds in Glasgow and Newcastle. Overall around 30% of children reported having been exposed to illegal drugs and 3.9% had started to use illegal drugs. There was a significant difference in the level of illegal drug use between our two cities. In most cases the illegal drug use identified on the part of preteens related to cannabis although in a small number of instances children were using heroin, cocaine and LSD. On the basis of this research we estimate that around 60 children in the ten to twelve age range will have used heroin in Glasgow and around 34 pupils will have used the drug in Newcastle. Preteen drug use was significantly associated with frequent smoking and alcohol consumption, with preteens' involvement in a range of problem behaviours, and with family difficulties including the presence of someone else within the family using illegal drugs. The paper concludes by noting some of the challenges that are likely to be faced by services seeking to support children who are using illegal drugs by their preteens.     

A WINNING COMBINATION: WOMEN,LITERACY, AND PARTICIPATION IN HEALTH CARE

Health information materials written at the appropriate reading level help individuals manage their own health care. In this study, we assessed the reading ability of clients and readability of the patient information materials at a rural women's health clinic. We administered a reading comprehension test to 50 subjects and tested the patient education materials using a readability formula. More than one in six women could not read all of the patient information, which could limit their understanding, and achievement of good health care. Commercially available materials can be checked readily for reading level using software installed in most computers. This software also allows clinicians who prepare their own materials for their patients to generate versions that are appropriate for different reading levels.     

Structural polymorphism of glycophorins demonstrated by immunoblotting techniques

We have explored the polymorphism of the glycophorin system in the human erythrocyte membrane using the immunoblotting techniques and examining 52 individuals selected without prior bias as to their serologic state and ten documented serologic variants of M, N, S, s blood group system. Polyclonal antisera to alpha glycophorin and to alpha glycophorin CNBr carboxyl terminal fragment C (residues 82-131) and M and N specific monoclonal antibodies (MoAbs) were used. The first two reagents detect specific regions of the alpha glycophorin molecule and all electrophoretically resolved species of glycophorins immunologically related to alpha and delta glycophorins (delta glycophorin, [alpha-delta] hybrids and other glycophorins with an alteration in the carboxyl terminal segment); the M and N MoAbs identified the glycophorin species containing or lacking the M or N determinant in the amino terminal octapeptide structures. We find that immunoblotting confirmed in all cases the serologically determined phenotype; we also find that polymorphic forms of the glycophorin system are relatively infrequent; immunoblotting, independent from serologic testing, was capable of detecting five mutants, two most likely S-s-U-phenotypes; a new glycophorin species was detected in normal red cells with both antiglycophorin and antipeptide C sera, which is not evident with MoAbs; immunoblots of known glycophorin variants (En(a-), U-, Mg, Mi I, II, III, V, and Sta) confirmed but also extended our knowledge of the abnormal glycophorins involved; and the He+ and Wrb(-) cells showed normal patterns.     

Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.     

Meal stimulation of cortisol secretion: a protein induced effect

Cortisol and ACTH secretion was studied in 52 healthy subjects who were fasted of fed various diets: standard, high fat, high carbohydrate, high protein. Subjects fed high protein diet (4 gm/kg body weight) showed significant increases in cortisol both at 30 and 60 min after the 1200 hr meal and 30 min after the 1600 hr meal. Increases in cortisol, of a smaller magnitude, were also seen after both the 1200 and 1600 hr meals in each of the diets with 1 gm protein/kg body weight (standard, high fat, high carbohydrate). ACTH was significantly increased following the 1200 hr and 1600 hr meals with the high protein diet. We conclude that dietary protein plays an important role in meal stimulated cortisol release.