Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation.

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active ß-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear ß-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach.

ß-Catenin activation synergizes with PTEN loss to cause bladder cancer formation.

Although deregulation of the Wnt signalling pathway has been implicated in urothelial cell carcinoma (UCC), the functional significance is unknown. To test its importance, we have targeted expression of an activated form of ß-catenin to the urothelium of transgenic mice using Cre-Lox technology (UroIICRE(+) ß-catenin(exon3/+)). Expression of this activated form of ß-catenin led to the formation of localized hyperproliferative lesions by 3 months, which did not progress to malignancy. These lesions were characterized by a marked increase of the phosphatase and tensin homologue (PTEN) tumour suppressor protein. This appears to be a direct consequence of activating Wnt signalling in the bladder as conditional deletion of the adenomatous polyposis coli (Apc) gene within the adult bladder led rapidly to coincident ß-catenin and PTEN expression. This PTEN expression blocked proliferation. Next, we combined PTEN deficiency with ß-catenin activation and found that this caused papillary UCC. These tumours had increased pAKT signalling and were dependent on mammalian target of rapamycin (mTOR). Importantly, in human UCC, there was a significant correlation between high levels of ß-catenin and pAKT (and low levels of PTEN). Taken together these data show that deregulated Wnt signalling has a critical role in promoting UCC, and suggests that human UCC that have high levels of Wnt and PI3 kinase signalling may be responsive to mTOR inhibition.

Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol.

Mutations in the adenomatous polyposis coli (APC) tumour suppressor are the key initiating event of colorectal cancer. Although the control of WNT signalling is well established as a central tumour-suppressive function, the significance of APC in regulating chromosome instability is less well established. In this study, we test whether APC-deficient cells have a functional spindle assembly checkpoint (SAC) in vivo by examining the response of these cells to Taxol and Vinorelbine. We also show for the first time that APC deficiency compromises the arrest response to Taxol in vivo. This effect is independent of the role that APC has in WNT signalling. At higher levels of Taxol, APC-deficient cells arrest as efficiently as wild-type cells. Importantly, this dose of Taxol strongly suppresses intestinal tumourigenesis in models of benign (APC(Min/+) mouse) and invasive (AhCreER(+)APC(fl/+)PTEN(fl/fl)) cancer. In contrast to intestinal enterocytes with a general SAC defect because of Bub1 (budding uninhibited by benzimidazole 1) deletion, APC-deficient enterocytes arrest equivalently to wild type when treated with Vinorelbine. This suggests that the failed arrest in response to Taxol is because of a specific defect in microtubule stabilization following Taxol treatment rather than a general role of the APC protein in the mitotic spindle checkpoint. In summary, this study clarifies the role of APC as a mitotic spindle checkpoint protein in vivo and shows that APC-deficient cells have a compromised response to Taxol.

[Bi-layer hernioplasty in day surgery]. / Hernioplastia în bi-strat în chirurgia de zi.

Nowadays the modern surgical techniques of hernia repair highly consider not only the decrease of the recurrence rate, but also a fast recovery, minimal postoperative pain and low costs of this type of surgery. This paper presents the preliminary results of a study performed on 41 patients diagnosed with inguinal hernia and operated under local anesthesia, as day surgery cases, during 2004-2006. The selection of the patients was performed under the "Guidelines and Standards for Day Surgery in Australia". We used local "step by step" anesthesia with a solution of 20 ml of lydocaine 1%, 20 ml of marcaine 0.5% and and 20 ml of NaCl 0.9%. The surgical procedure based on the sutureless technique "Gilbert", implied the placement of two polypropylene meshes: one of them introduced through the deep inguinal ring, and the other one in the inguinal channel, minimally fixed. We studied: intraoperative comfort and postoperative pain of the patients, problems related to the surgical technique, the operative time, complications and the recurrence rate. The follow-up period was 14 months. 85.36% of the patients had a very good intraoperative comfort, and only 14.64 % of them needed supplementary intravenous analgesia; none of the patients needed conversion to general anesthesia. The mean operative time was 65 minutes. The complications were: seroma (3 patients) and hematoma (1 patient), all of them treated conservatively. No recurrence was noticed. From this preliminary study it seems that the surgical treatment of the inguinal hernia with double polypropylene mesh, under local anesthesia and as day surgery is feasible and secure. The minimal postoperative complications and the patients' satisfaction show that the new concept of day surgery must be promoted in our surgery clinics. However, we must emphasize that, in order to obtain good results on a larger scale, certain measures are mandatory, such as: organizing a special area and circuits for day surgery, nursing at home, precise inform of the patients (video samples), the use of modern communication (internet) with patients.

[The place of surgery in the complex treatment of gastric cancer]. / Locul chirurgiei în tratamentul complex al cancerului gastric.

The fact that the first symptoms of gastric cancer occur when therapy, even surgical, is limited to palliative objectives, was the starting point of the present study. A clinical study was carried out in a group of 158 patients with gastric cancer admitted to the Surgical Clinic II of Cluj-Napoca in the past 10 years. The most frequent location of the gastric neoplasm was the antrum-pylorus, though there were also extended tumours that invaded the neighbouring organs. Secondary processes were evidenced in over 70% of the patients studied. This fact, together with the associated conditions, made us limit the gastric resection even for the cases in which we considered total extensive gastrectomy to be the best solution. The methods of restoration of the gastric passage were esophago-jejunostomy on the Y loop in the first place, followed by gastro-jejunostomosis with the other techniques of gastric reconstruction. Palliative procedures such as gastro-enteroanastomosis or nutritional gastro-jejunostomy were sometimes necessary. Good postoperative results were obtained in 69% of the patients, which emphasizes once again the importance of this study.

[Clinical study of the efficacy of albendazole treatment in human hydatidosis]. / Studiu clinic al eficientei tratamentului cu albendazol în hidatidoza umana.

A follow-up study of Albendazol effectiveness therapy in human hydatid diseases was carry out using WHO methodology. Albendazole was given at a dose of 10 mg/Kg body/day in cycles of 28 days separated by 14 days without treatment. The efficacy of chemotherapy was evaluated by clinical improvement and changes in the cyst's morphology (detachment and collapse of the cyst membrane and increased density of the cyst fluid). We performed this study in 134 patients with hydatidosis: 17 patients with pre and post surgery treatment, 50 patients with post surgery treatment and 67 patients with chemotherapy only. Albendazole was effective in the hydatid disease; the patients with complex chemotherapy treatment did not report any secondary hydatidosis during the follow-up period (max. 2 years); the patients with exclusive chemotherapy reported 79% successful response, only 21% of them remained with unchanged cyst's size, but with modified internal structure. The therapeutic response depends of the cyst's size and its visceral site.

Chronic methanesulfonyl fluoride enhances one-trial per day reward learning in aged rats.

Aged (24-month-old) rats were treated chronically with methanesulfonyl fluoride (MSF), an acetylcholinesterase (AChE) inhibitor with selectivity for central nervous system AChE, or with injection vehicle alone. Twelve 0.22 mg/kg IP injections were given over 4 weeks. MSF rats showed significantly greater speed and accuracy on a 1 trial/day discriminative reward learning task. The chronic MSF treatment resulted in a 56% decrease in brain AChE activity but no discernable locomotor side effects and no liver damage as indicated by aspartate transferase activity.

[The elderly and the transition to a market economy in Romania. Discriminating attitudes vis-a-vis the elderly]. / Populatia varstinica si tranzitia la economia de piata in Romania. Atitudini de discriminare a populatiei varstnice.

PIP: Population aging has started late in Romania but has increased rapidly in the last few decades. The share of the population aged 60 and over reached 17% in 1992 and the decline in fertility after 1989 will considerably increase this share in the future. The author provides a detailed analysis of the present economic and social situation of the elderly in Romania. Factors such as the economic crisis, and particularly the deterioration of the standard of living, the very low income (pension) level, the high rate of inflation, and the lack of appropriate medical care have pushed most of the aged population into poverty. According to recent surveys, 1.5 million people out of the 3.8 million aged 60 and over live below the poverty line.^ieng

Galanin attenuates retention of one-trial reward learning.

Galanin is a neuropeptide that coexists with acetylcholine in the septohippocampal pathway. Galanin appears to have a negative modulating influence on cholinergic transmission, suggesting that it might interfere with memory formation on a one-trial discriminative reward learning task. The apparatus was a starburst maze with five radiating alleys, one an ascending baited alley. The subjects were 38 two to three month old Sprague-Dawley rats cannulated in the body of the lateral ventricles and deprived to 80% of initial weight. Ten rats were infused i.c.v. over six mins. with 8 micrograms galanin in 24 microliters saline and 10 with saline alone. Twenty mins. after completion of infusion, each rat was placed in the maze and observed under "blind" conditions for number of errors (blind alleys entered) and latency to reach reward. Each rat's speed score was 100 sec./latency. One day later, each rat was retested in the maze. Each rat's retention scores were its decrease in errors and increase in speed between the single training trial and the retention trial. Galanin infused rats showed significantly less retention by both measures. In a second experiment, either the same dose of galanin or saline alone was infused 20 mins. before the retention trial. There was no significant effect, suggesting that galanin may interfere with memory formation rather than memory retrieval or task performance.

Ultrastructural evidence for a possible differentiation way in the life-cycle of Blastocystis hominis.

The present paper is reporting the characteristic ultrastructural aspects of an amoeboid B. hominis population obtained from a child having giardiasis and dysentery in history. The particular features of smooth endothelial reticulum are postulated as being the expression of functional changes of this organelle in the differentiation process, the protozoon passing from the amoeba to the vacuolar form.

[Romania's post-revolutionary trends in permanent emigration]. / Principalele tendinte ale emigratiei definitive in Romania postrevolutionara.

PIP: The author analyzes trends in permanent emigration from Romania since the fall of the Ceaucescu government at the end of 1989. Emigrant characteristics are described.^ieng

[Clinical, diagnostic and therapeutic problems in the postthrombotic syndrome. Our experience]. / Probleme clinice, diagnostice si terapeutice în sindromul posttrombotic. Experienta noastra.

An analysis is presented, of the experience acquired in the II-nd Surgical Clinic of Cluj-Napoca in connection with 150 cases of postthrombotic syndrome followed and treated over the last 5 years (1983-1987). Considerations are made concerning terminology, and evaluation of diagnostic and therapeutic means applied. The post-thrombotic syndrome develops in a variable interval after the thrombophlebitis (months and even years). A series of factors prevent of enhance the development of the syndrome (98% diagnostic errors and therapeutic failures). Phlebography is mandatory in cases where surgery is considered. Noninvasive explorations (Doppler, plethysmography) limit the use of phlebography. The most efficient treatment is prophylaxis (consisting in the prophylaxis and the correct treatment of thromboembolic disease). The usual treatment is mainly medical and conservative (59.4%). Surgery is carried out in cases where the superficial, the communicating and the deep venous systems are involved.

[A comparative study of coprological methods for identifying Cryptosporidium spp. oocysts]. / Studiu comparativ al metodelor coprologice de identificare a oochisturilor de Cryptosporidium spp.

With a view to optimize the etiological diagnosis of diarrhoea the authors have attempted to improve the diagnostic methodology for the parasite Cryptosporidium spp. as a current general technique, as well as a screening technique. A comparative evaluation of the various methods used for the concentration and the staining of cysts of Cryptosporidium spp. was done after quantification according to a five parameter score: electiveness, morphology, chromatic contrast, rapidity and accessibility. The importance of the screening tests in the diagnosis of cryptosporidiosis was evaluated according to indicators such as sensitivity, specificity and predictive value. The maximal general score (17) was obtained with the modified Ziehl-Neelsen stain which was both sensitive and viable, and was used as a method for the confirmation of the presence of the parasite. With regard to the screening methods rapid techniques employing methylene-blue and/or fuchsine gave indicator values between 76% and 83%. The best results were obtained when samples were enriched with the aid of concentration techniques. It is appreciated that the concomitant and repeated use of two techniques of diagnosis, a rapid one and a confirmation technique aimed at demonstrating the presence of Cryptosporidium cysts allows a competent parasitological diagnosis of cryptosporidiosis.

Cryptosporidiosis in children and adults: parasitological and clinico-epidemiological features.

By using the elective diagnosis methodology for Cryptosporidium (modified Ziehl-Neelsen and Heine stainings), 481 faeces samples from patients--children and adults--presenting acute or prolonged gastroenteritis and also from asymptomatic ones, but with professional, immunological or pharmacological risk for infection, were studied. Twelve Cryptosporidium positive cases were identified, meaning a general prevalence of 2.48% Cryptosporidium infection was detected in all investigated epidemiological groups: children, animal handlers, immunodeficient patients, immunocompetent adults with acute gastroenteritis. The risk factors hierarchy elicited the role of children collectivities attending, for acquiring the parasite in infantile cryptosporidiosis, while the opportunistic and zoonotic feature of the disease was especially present in adults' cryptosporidiosis. The assessment of cryptosporidiosis evolution, according to patients' immune status, has not allowed an obvious clinical discrepancy, since the immunocompetent subjects with professional risk had presented a prolonged oocysts excretion. The different clinico-epidemiological and parasitological features of Cryptosporidium infection are commented and the importance of applying Cryptosporidium methodology in current diagnosis practice is emphasized.

[Venous emergencies. Personal experience and viewpoint]. / Urgences veineuses. Expérience et attitude personnelles.

Based on a casuistic report of 226 cases, the authors propose a classification of venous emergencies, including acute deep thrombo-phlebites (with their anatomo-clinical and topographical varieties), the complications of varicose disease, venous traumatism and anorectal venous thrombosis. The authors touch on problems associated with clinical and paraclinical diagnosis, prophylaxis and active surgical therapy, respectively thrombectomy, ligation of the long saphenofemoral junction, the treatment of varico-phlebitis and urgent traumatic lesions, the thrombectomy and radical cure of haemorrhoids. The coupling of any of these affections presents a potential of great seriousness, sometimes a major vital risk which necessitates immediate therapeutic intervention. The classification of the idea of "venous emergency" in comparison with that of "arterial emergency", is outlined, and the authors mention that a surgical treatment in these affections is to be preferred.