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.     

Lignocaine gel used for lubrication of intranasal and endotracheal tubes in premature neonates

Bendixen D, Halvorsen A-C, Hjelt K, Flachs H. Lignocaine gel used for lubrication of intranasal and endotracheal tubes in premature neonates. Acta Prediatr 1994;83:493–7. Stockholm. ISSN 0803–5253
In this study, we have measured the plasma concentration of lignocaine and its metabolite, monoethylglycinxylidin, in 19 premature neonates (gestational age 33 weeks) when lignocaine gel was used for lubrication of an intranasal tube (during continuous positive airway pressure treatment) or an endotracheal tube (for intubation). We did not find any correlation between plasma concentration of lignocaine or monoethylglycinxylidin and weight of the infant (range 795–2530 g). None of the neonates had toxic levels of lignocaine. One neonate had an exceptionally high but not toxic plasma level of monoethylglycinxylidin. However, this neonate had been treated for severe seizures with an iv infusion of lignocaine up to 13 h before the study. In conclusion, we found it safe to use moderate amounts of lignocaine (i.e. 0.3 ml/kg of lignocaine gel 20 mg/ml) for lubricating both intranasal and endotracheal tubes.     

Prognostic significance of p16 and CDK4 proteins in localized prostate carcinoma

BACKGROUND: In prostate carcinoma, a very low frequency of point mutations of the tumor suppressor gene CDKN2/MTS1 (p16(INK4) ) has been reported, but deletions of 9p21 and inactivation by promoter methylation are observed more frequently. In the current study the authors evaluated the expression of p16 and CDK4 proteins and their prognostic significance in patients with clinically localized prostate carcinoma. METHODS: The levels of p16 and CDK4 proteins were quantitated by immunofluorescence flow cytometry, using paraffin embedded material, in 104 adenocarcinomas of the prostate after radical prostatectomy. These levels then were compared with 25 cases of benign prostate hyperplasia (BPH). RESULTS: In prostatic carcinoma specimens, p16 protein was elevated significantly compared with BPH, with a median fluorescence index (FI) of 15.4 versus 10.7, respectively (P = 0.010). This was not the case for CDK4 protein, although p16 protein expression correlated significantly with CDK4 protein expression in BPH (Spearman rank correlation [R(S)] = 0.63) and carcinoma (R(S) = 0.78). In univariate survival analysis of the first 5 years, high levels of p16 protein expression (FI > 11.7) (P = 0.005), tumor greatest dimension, World Health Organization (WHO) histologic grade, capsular penetration, seminal vesicle invasion, positive surgical margins, lymph node involvement, and preoperative serum prostate specific antigen > 20 ng/mL all were significant predictors of biochemical failure. In multivariate survival analysis, high p16 protein expression (P = 0.015), age, WHO histologic grade, capsular penetration, and seminal vesicle involvement remained as independent predictors of biochemical failure. CONCLUSIONS: These data suggest that increased expression of p16 protein, but not CDK4 protein, may be involved in the development of prostate carcinoma and may represent an independent predictor of biochemical failure after radical prostatectomy.     

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)