Ouabain exacerbates activation-induced cell death in human peripheral blood lymphocytes

Lymphocytes activated by mitogenic lectins display changes in transmembrane potential, an elevation in the cytoplasmic Ca2+ concentrations, proliferation and/or activation induced cell death. Low concentrations of ouabain (an inhibitor of Na+,K+-ATPase) suppress mitogen-induced proliferation and increases cell death. To understand the mechanisms involved, a number of parameters were analyzed using fluorescent probes and flow cytometry. The addition of 100 nM ouabain to cultures of peripheral blood lymphocytes activated with 5 microg/ml phytohemagglutinin (PHA) did not modify the increased expression of the Fas receptor or its ligand FasL induced by the mitogen. However, treatment with ouabain potentiated apoptosis induced by an anti-Fas agonist antibody. A synergy between ouabain and PHA was also observed with regard to plasma membrane depolarization. PHA per se did not induce dissipation of mitochondrial membrane potential but when cells were also exposed to ouabain a marked depolarization could be observed, and this was a late event. It is possible that the inhibitory effect of ouabain on activated peripheral blood lymphocytes involves the potentiation of some of the steps of the apoptotic process and reflects an exacerbation of the mechanism of activation-induced cell death.     

More differences between HNPCC-related and sporadic carcinomas from the endometrium as compared to the colon

PURPOSE: Recognition of hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial carcinoma from sporadic carcinoma by histologic features as compared with colonic cases. STUDY DESIGN: Case-control study. METHODS AND MATERIALS: From the files of the Nijmegen Hereditary Cancer Clinic, HNPCC-related (n = 6) endometrial and colorectal (n = 18) carcinomas were selected. For every HNPCC-related tumor, 2 sporadic control cases were included. The tumors were evaluated for the following 7 pathologic features: tumor differentiation, T-stage, growth pattern, presence of Crohn-like lymphoid reaction, mucinous differentiation, presence of lymphangioinvasive growth, and the amount of tumor-infiltrating lymphocytes. RESULTS: HNPCC-related endometrial carcinomas were significantly more often poorly differentiated (83% versus 27%), more often showed the presence of a Crohn-like lymphoid reaction (100% versus 13%) and lymphangioinvasive growth (67% versus 0%), and high number of tumor-infiltrating lymphocytes were more often present (100% versus 36%) compared with sporadic endometrial carcinomas. The differences between HNPCC and sporadic colorectal cancer specimens were less discriminating. CONCLUSIONS: HNPCC-related endometrial carcinomas are characterized by poor differentiation, more frequent Crohn-like lymphoid reaction, lymphangioinvasive growth and more tumor-infiltrating lymphocytes. These features therefore might form the basis for selecting patients for counseling in a hereditary cancer clinic or testing for microsatellite instability or mutation analysis of mismatch repair genes, especially when they are of relatively young age.     

Surgical anatomy of the midface as applied to facial rejuvenation

Distinct anatomic structures provide attachments and support for the soft tissues of the central third of the face. Over time, laxity of these structures and descent of the malar fat pad contribute to the characteristic changes seen in the aging face. Mobilization of the midface soft tissues to allow reelevation of the malar fat pad is an effective method of rejuvenating the midface. A focused anatomic dissection of 8 fresh cadaver heads was performed to evaluate 4 soft-tissue structures that control mobilization of the malar fat pad. Specifically, the orbicularis retaining ligaments, the lateral orbital thickening, prezygomatic space, and zygomatic cutaneous ligaments were evaluated. The anatomic relationship of these structures explains the visible effect of aging in the central third of the face. In addition, it correlates with the outcomes of surgical rejuvenation as demonstrated in clinical cases. Effective repositioning of the malar fat pad was found to be reliably obtained by release of the lateral orbital thickening and the orbital retaining ligaments. Suspension of the malar soft tissue is in a cephalad direction after release of these structures recreates a youthful facial architecture. Motor nerve injury is less likely to occur with this technique than with traditional lateral facelift approaches. The conclusion reached is that ptosis of the malar fat pad can be corrected safely and effectively utilizing either the lower lid blepharoplasty approach or temporal prehairline incision. These findings were consistent with clinical data from facial rejuvenation procedures.     

Two different therapeutic regimes in patients with sequelae of hemolytic-uremic syndrome

Renal disease is the most important long-term complication of hemolytic-uremic syndrome (HUS). A comparative study of renal function was carried out in two groups of patients. Group 1 included 19 children followed for a median of 11 years, 1960–1980, with a low-sodium diet, antihypertensive drugs, and a restricted protein intake in the end stage of renal disease. Group 2 included 26 children treated for a median of 9 years, 1988–2002, on a low-sodium diet, early restriction of protein intake according to recommendations, and angiotensin converting enzyme inhibitors (ACEi). Long-term renal function was assessed by the inverse of the plasma creatinine concentration (1/[Cr]) over time. Linear regression lines were fitted to individual values of 1/[Cr] for each child. Regression coefficients of children in group 1 were all negative, ranging from –0.031 to –0.00043; 7 were significantly different from zero, indicating a linear fall in renal function over time. In contrast, children from group 2 had 11 negative slopes (only 1 significant) and 15 positive slopes, ranging from 0.17893 to –0.3899. Fishers exact test showed that group 1 had significantly more children with negative slopes than group 2. This comparatively better long-term outcome of renal function in children under contemporary treatment was probably associated with early restriction of protein and use of ACEi.     

Impact of interpreters' approach on Latinas' use of amniocentesis.

Communication difficulties in multicultural clinical settings can be exacerbated by translators, but their actual impact on medical decisions has not been systematically evaluated. This study sought to determine the influence of translators participating in clinical encounters in which English-speaking clinicians offered amniocentesis to Spanish-speaking women by conducting systematic observations of 61 prenatal genetic consultations and recording translators' training and background characteristics and patients' amniocentesis decisions. Translators' behavioral styles were classified according to 10 inductively determined criteria. Translators' approaches were classified as Distant, Authoritative, or Missionary. Whereas the first category remained emotionally detached, the others sought to build rapport and trust with the patient. Quantitative analysis revealed statistically significant associations between translation styles that sought to engender trust and likelihood the pregnant woman agreed to amniocentesis. The authors conclude that translators' affective approaches can influence whether patients accept or decline amniocentesis.     

Graph models for phenotype and genotype association between oral mucosa and submandibular gland tumorigenesis in rat

Background:  In recent years, success of statistics in field of genetics has been the identification of genes that affect the process of disease. Experimental models using animals enable early stages of tumor development to be studied. The aim of this study was to apply graph models to assess the association between the observed phenotypic changes in rat oral mucosa and induced tumorigenesis in the submandibular gland (SMG).
Materials and methods:  We studied changes in oncogenes TP53 and bcl-2, histopathological and immunomarker variables in samples of oral mucosa and SMG of Wistar male rats, 60 days old and 180 g in weight, in which tumorigenesis was induced in their SMG by a 0.5% solution of 9,10-dimethyl-1,2-benzanthracene in acetone. A set of linear structural equations were defined, with each formula indicating the response variables and the direct influences. In graph models, saliva was considered as a latent variable. The association was analyzed using Graphical Gaussian Markov models and odd ratios.
Results:  About 40% of animals treated with 9, 10-dimethyl-1, 2-benzanthracene showed histological alterations in the epithelial basal strata of their oral mucosa only at 150 days. Statistical models indicated a relationship between gene alteration in gene bcl-2 in the SMG and histological changes observed in the oral mucosa ( P  = 0.04).
Conclusion:  Graph statistical model with one latent variable allows to conclude that these results associated with other clinical parameters may be useful in detecting early changes in SMG tumorigenesis. Furthermore, the design of randomized sampling of oral mucosa allows to validate these results and establish a reliable methodology for presumptive diagnosis or screening in the future.     

Intradural lipoma in a child.

We report the case of a 5-year-old Nigerian boy in whom conus medullaris and cauda enquina compression was due to an intradural lipoma, a rare tumour of the spinal canal in the tropics. The literature on the subject is briefly reviewed and the differential diagnoses are discussed. The occurrence of the lesion in this child, without other features of spinal dysraphism, is noteworthy.