Assessment of risk factors for emergence distress and postoperative behavioural changes in children following general anaesthesia

BACKGROUND: Emergence distress commonly occurs in children recovering from the immediate effects of general anaesthesia. This study was performed to (1) examine whether parental presence in the operating room during emergence from anaesthesia reduces the incidence or severity of emergence distress behaviour, and (2) assess psychosocial risk factors, including child temperament and sleep behaviour, for development of emergence distress. METHODS: A randomized and controlled trial of parental presence at emergence was conducted in 100 ASA class I and II children having general anaesthesia for inguinal or penile surgery. Children in the study group had a parent present at induction and emergence of anaesthesia, while children in the control group had a parent present only at induction. Emergence and postanaesthesia care unit (PACU) behaviour was monitored using both the Operating Room Behaviour Rating Scale (ORBRS) and a 7-point Likert type cooperation scale. RESULTS: One-way anovas showed no significant differences between the control group and the study group on emergence distress behaviour. The frequency of negative postoperative behavioural changes at 1 and 4 weeks postsurgery was low in both groups. Children described as clingy/dependent (chi2 = 5.57, P < 0.06) and children with frequent temper tantrums (chi2 = 7.44, P < 0.02) were more likely to have emergence distress behaviour. CONCLUSIONS: Parental presence during emergence from anesthesia did not decrease the incidence or severity of emergence distress behaviour in children. Young children and children with a history of temper tantrums or separation anxiety may be more likely to develop such behaviour.     

Biological, histological, and clinical impact of preoperative IL-2 administration in radically operable gastric cancer patients

BACKGROUND AND OBJECTIVES: Surgery induces lymphocytopenia and this decrease of host defenses, related to interleukin-2 (IL-2) endogenous imbalance during postoperative period could promote the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. Moreover, tumor infiltrating lymphocytes (TILs), activated by endogenous IL-2 release, are linked to prognosis in cancer patients. The aim of this randomized study is to assess the biological (peripheral blood cells count, related to the grade of immunosuppression), histological (TILs), and clinical (overall and disease-free survival) impact of preoperative low doses administration of IL-2 in patients with radically operable gastric cancer. METHODS: This prospective study enrolled 69 consecutive patients with histologically proven gastric adenocarcinoma who underwent radical surgery from October 1999 to December 2002 (M/F 39/30; mean age 66; range 42-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (35 patients) or surgery plus preoperative treatment with recombinant human IL-2 (34 patients). We considered the total lymphocyte count and lymphocyte subset (CD4, CD4/CD8) during the preoperative period, before IL-2 administration, and on the 14th and 50th day, peritumoral stromal (fibrosis) reaction, neutrophils, lymphocytes, and eosinophils infiltration in tumor histology, and morbidity disease free and overall survival were evaluated. RESULTS: Two groups were well matched for type of surgery and extent of disease. All the patients underwent radical surgery plus D2 lymphadenectomy. At baseline, there were no significant differences in total lymphocyte and lymphocyte subsets between groups. The control group showed a significant decrease of total lymphocytes, CD4 cells, and CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. In the control group 65% of patients had a decrease of CD4 under 500 cells/mmc. Instead it has been observed in IL-2 group a significant increase over the control group values of total lymphocytes and CD4 cells (14th total lymphocytes and CD4: IL-2 vs. control P < 0.05). Moreover in this group only 15% patients had CD4 under 500 cells/mmc. This difference, in CD4 count, is significant even at the 50th postoperative day (P = 0.006). IL-2 group showed lower postoperative complications (2/34 vs. 11/35; P < 0.05), and higher lymphocyte/eosinophil infiltration into the tumor (P < 0.0002). Median follow-up was 26 months (range 10-48) and median overall and disease-free survivals were longer, even if not significantly, in the IL-2 group than in the control arm (P = 0.07 and P = 0.06 respectively). CONCLUSIONS: This randomized study would suggest that a preoperative immunotherapy with IL-2 is a well-tolerated treatment able to prevent surgery-induced lymphocytopenia. IL-2 seems to neutralize the immunosuppression induced by operation and so to stimulate the host reaction against tumor tissue (lymphocytes/eosinophils infiltration). Furthermore IL-2 seems to have an impact on clinical course reducing morbidity of surgery and ameliorating overall and disease-free survival.     

Application of the model for end-stage liver disease score for transjugular intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites and renal impairment

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) can manage severe complications of portal hypertension. The Mayo Clinic group proposed a so-called model for end-stage liver disease (MELD) to predict survival in cirrhotic patients. High creatinine levels determine a decrease in calculated survival chances with MELD but functional renal disease can be reversed by TIPS. The aim of this study was to evaluate the efficacy of MELD in predicting survival after TIPS, particularly in patients with refractory ascites associated with functional renal failure. METHODS: This retrospective analysis examines 68 cirrhotic patients who underwent elective TIPS: 48 patients had refractory ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis was used to establish predictive parameters of survival after TIPS. Kaplan-Meier and log-rank tests were used to compare survival rates observed in our patients with those evaluated with the MELD score. RESULTS: The age of patients was the only variable shown to have an independent value in predicting survival after TIPS. In patients undergoing shunting for refractory ascites, the survival rates at 6, 12 and 24 months after the procedure were significantly higher than expected with the MELD score. CONCLUSIONS: The MELD scale may underestimate the efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and functional kidney dysfunction. Further studies are needed to confirm this finding and ultimately to assess a correction factor to better predict survival after TIPS in patients with functional renal impairment.     

Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease

Mutations in complement factor H (HF1) gene have been reported in non-Shiga toxin-associated and diarrhoea-negative haemolytic uraemic syndrome (D-HUS). We analysed the complete HF1 in 101 patients with HUS, in 32 with thrombotic thrombocytopenic purpura (TTP) and in 106 controls to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and non-mutation carriers and the role of HF1 polymorphisms in the predisposition to HUS. We found 17 HF1 mutations (16 heterozygous, one homozygous) in 33 HUS patients. Thirteen mutations were located in exons XXII and XXIII. No TTP patient carried HF1 mutations. The disease manifested earlier and the mortality rate was higher in mutation carriers than in non-carriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in non-mutated patients half of the grafts were functioning after 1 year. Three HF1 polymorphic variants were strongly associated with D-HUS: -257T (promoter region), 2089G (exonXIV, silent) and 2881T (963Asp, SCR16). The association was stronger in patients without HF1 mutations. Two or three disease-associated variants led to a higher risk of HUS than a single one. Analysis of available relatives of mutated patients revealed a penetrance of 50%. In 5/9 families the proband inherited the mutation from one parent and two disease-associated variants from the other, while unaffected carriers inherited the protective variants. In conclusion HF1 mutations are frequent in patients with D-HUS (24%). Common polymorphisms of HF1 may contribute to D-HUS manifestation in subjects with and without HF1 mutations.     

Bone marrow extracellular large geometric crystals in IgG/lambda MGUS

We describe the peculiar histopathology of the bone marrow in a case of IgG/lambda MGUS. Striking eosinophilic crystals with a rectangular, rhomboid or square shape lay in the interstitium, sometimes in optically empty spaces, but failed to elicit a foreign body giant cell reaction. Their histochemical properties, immunoreactivity for anti-lambda light chain antiserum, and ultrastructural features strongly supported their relationship with the paraprotein synthesized by the monoclonal plasma cells. The crystals were not observed on bone marrow aspirate smear, suggesting that they had formed during trephine biopsy processing or, alternatively, that they had been removed during the smear preparation. We feel that pathologists should be aware of the existence of this type of crystals, which differ from both the amyloid deposits and the proteinaceous material sometimes observed in plasma cell proliferations. Their presence in the bone marrow should alert the clinician to investigate the involvement of other organs with immunoglobulin deposits.     

The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines

Alterations of 19q13 are frequently observed in glial neoplasms, suggesting that this region harbors at least one gene involved in gliomagenesis. Following our previous studies on structural 19q chromosome rearrangements in gliomas, we have undertaken a detailed FISH analysis of the breakpoints and identified a 19q13.2 intrachromosomal amplification of the MAP/microtubule affinity-regulating kinase 4 (MARK4) gene in three primary glioblastoma cell lines. Recent data suggest that this gene is involved in the Wnt-signaling pathway. We observed that the expression of the alternatively spliced MARK4L isoform is upregulated in both fresh and cultured gliomas and overexpressed in all of the above three glioblastoma cell lines. Interestingly, we also found that MARK4L expression is restricted to undifferentiated neural progenitor cells or proliferating glial precursor cells, whereas its expression is downregulated during glial differentiation. Perturbation of expression using antisense oligonucleotides against MARK4 in glioblastoma cell lines, consistently induced a decreased proliferation of tumor cells. Taken together, these data show that MARK4, which is normally expressed in neural progenitors, is re-expressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements.     

Central granular cell odontogenic tumour: report of the first malignant case and review of the literature

Granular cell odontogenic tumours (GCOT) are rare neoplasms that usually manifest a benign clinical behaviour. We document the first case of GCOT exhibiting clinico-pathological features of malignancy that occurred in the maxilla of a 40-year-old male. The lesion appeared as an intra-oral polypoid mass and, at CT scan, as a poorly demarcated radiolucency eroding the cortical plate. Histologically, the tumour consisted of clusters of granular cells, exhibiting nuclear pleomorphism, prominent nucleoli and mitotic figures, and spindle cells in a collagenous stroma containing cementicles and strands of odontogenic epithelium. Morphologic transition from fibroblast-like to granular cells was frequently detected. The tumour cells extensively invaded the oral and respiratory mucosae and the adjacent soft tissues and exhibited vimentin and CD 68 immunoreactivity and high (21%) Ki 67 immunolabeling but not cytokeratins, E.M.A. actin, desmin, myosin or S-100 protein positivity. The patient experienced tumour recurrence 16 months after radical surgery. While the histogenesis of GCOT remains to be clarified, we document the existence of a malignant counterpart of this tumour and propose the name of malignant GCOT or granular cell odontogenic sarcoma for such entity.     

Xrx1 controls proliferation and multipotency of retinal progenitors

We investigated the function of Xrx1 during Xenopus retinogenesis. Xrx1 overexpression lengthens mitotic activity and ectopically activates the expression of markers of undifferentiated progenitors in the developing retina. We assayed Xrx1 ability to support proliferation with a cell-autonomous mechanism by in vivo lipofection of single retinal progenitors. Xrx1 overexpression increases clonal proliferation while Xrx1 functional inactivation exerts the opposite effect. We also compared the effects of Xrx1 with those of the cyclin-dependent kinase cdk2, a strong mitotic promoter. Despite the similar increase in clonal proliferation displayed by both factors, Xrx1 and cdk2 act differently on retinal cell fate determination. cdk2/cyclinA2 lipofected retinas show a decrease in early-born cell types as ganglion cells and cones and an increase in late-born types such as bipolar neurons. On the contrary, Xrx1 lipofected retinas show no changes in the proportions of the different cell types, thus suggesting a role in supporting multipotency of retinal progenitors.