Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

A community based study of failure to thrive in Israel

OBJECTIVE: To examine the characteristics of infants suffering from failure to thrive in a community based cohort in Israel and to ascertain the effect of failure to thrive on their cognitive development. METHODS: By review of records maintained at maternal and child health clinics in Jerusalem and the two of Beit Shemesh, epidemiological data were obtained at age 15 months on a cohort of all babies born in 1991. For each case of failure to thrive, a matched control was selected from the same maternal and child health clinic. At age 20 months, cognitive development was measured, and at 25 months a home visit was carried out to assess maternal psychiatric status by questionnaire, and the HOME assessment was performed to assess the home environment. RESULTS: 3.9% of infants were found to have fallen below the third centile in weight for at least three months during the first year of life. Infants with failure to thrive did not differ from the general population in terms of obstetric or neonatal complications, birth order, or parents' ethnic origin, age, or years of education. The infants with failure to thrive did have lower birthweights and marginally smaller head circumferences at birth. Developmental assessment at 20 months of age showed a DQ of 99.7 v 107.2 in the matched controls, with 11.5% having a DQ below 80, as opposed to only 4.6% of the controls. No differences were found in maternal psychiatric problems as measured by a self report questionnaire. There were, however, significant differences in subscales of the HOME scale. CONCLUSIONS: (1) Infants who suffered from failure to thrive had some physiological predispositions that put them at risk; (2) failure to thrive may be an early marker of families providing suboptimal developmental stimulation.     

Wound bed preparation: a systematic approach to wound management

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or "stuck" at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management.
This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues;
• the current status of wound bed preparation;
• an analysis of the acute and chronic wound environments;
• how wound healing can take place in these environments;
• the role of wound bed preparation in the clinic;
• the clinical and cellular components of the wound bed preparation concept;
• a detailed analysis of the components of wound bed preparation.
(WOUND REP REG 2003;11:1–28)     

Hepatitis B surface protein docked vesicular carrier for site specific delivery to liver

The intrinsic liver tropism of liposomes can be augmented by the addition of targeting features such as the incorporation of hepatotropic elements of the hepatitis viruses. Hepatitis B virus is known to infect hepatocytes after viremia by asialoglycoprotein receptor mediated uptake. However, the specificity of hepatitis B virus surface protein (HBsAg) towards hepatocytes has confronting reports. In the present study, we evaluated the functional ability of HBsAg to be employed as a ligand for targeting hepatocytes. We prepared (14)C labeled small unilamellar vesicles (SUVs) composed of egg PC/Cholesterol/N-glutarylphosphatidylethanolamine (NGPE) in a 60:30:10 molar ratio. HBsAg was covalently linked to SUVs using a water-soluble carbodiimide (EDC) mediated conjugation with NGPE. In vitro cell binding and uptake studies revealed that bioprotein docked carrier system was efficiently taken up by HepG2 cells by the receptor mediated endocytosis. The biodistribution behaviour of plain and HBsAg coated liposomes was also examined followed by intravenous injection. The study revealed that almost 75% of the radioactivity was recovered in the liver after 4 h of injection that was nearly three-fold greater in magnitude than the plain liposomes. Further, fractionation of liver into liver parenchymal cells (PC) and non-parenchymal cells confirmed the preferential localization of the HBsAg coated liposomal carrier in the parenchymal cells.     

Relapsing polychondritis studied by computed tomography

Computed tomographic findings in a patient with relapsing polychondritis are described. Collapse of the cartilage of the nose and calcification in cartilages of the ears were clearly demonstrated. CT scanning was also helpful in evaluating the tracheobronchial tree for airway compromise, which could prove fatal in this condition.     

Colo-colonic intussusception caused by a solitary Peutz-Jeghers polyp

A case of acute large bowel obstruction by colo-colonic intussusception in a healthy 19-year-old man is presented. The lead point of the intussusception is a rare solitary colonic Peutz-Jeghers polyp in the descending colon of a man without the full Peutz-Jeghers syndrome. The clinical presentation, imaging findings on plain radiographs, single contrast enema and CT, and findings at colonoscopy and surgery are correlated with pathology results and a brief review of the literature.     

Detecting fetomaternal hemorrhage after first-trimester abortion with the Kleihauer-Betke test and rise in maternal serum alpha-fetoprotein

OBJECTIVE: To compare the incidence and detect the volume of fetomaternal hemorrhage (FMH) during first-trimester abortion with the Kleihauer-Betke test (KBT) and rise in maternal serum alpha-fetoprotein (AFP). STUDY DESIGN: Blood samples were drawn immediately before and after first-trimester termination of pregnancy in 48 women. AFP was estimated using an enzyme-linked immunosorbent assay technique. Fetal cells were counted using the acid elution technique described by Kleihauer. Volume of FMH with both techniques was calculated using standard formulae. Significant FMH was reported when there was a > 40% rise in AFP or > 0.25 mL bleed detected by KBT. RESULTS: Of the 48 cases studied, 18 (37.5%) showed no indication of FMH by either AFP or KBT. In 30 (62.5%) cases there was evidence of FMH; in 7 (14.6%) this was shown by both AFP and KBT. Another 10 (21%) showed significant changes in AFP concentration only, and 13 (27%) showed abnormal KBT results with stable AFP levels. The incidence of detectable FMH after first-trimester abortion in this series was 35% when assessed by AFP and 42% when assessed by KBT (P > .05). The mean volume of FMH detected by KBT was 0.5+/-0.05 mL and by AFP was 0.01+/-0.02 mL. CONCLUSION: This study showed that AFP and KBT are equally sensitive methods of detecting the incidence of FMH in first-trimester abortion, but concordance between the 2 tests is poor. The volume of FMH detected by KBT and FMH is also significantly different.