Intestinal bacterial translocation and tight junction structure in acute porcine pancreatitis

Background/Aims: To examine whether intestinal bacterial translocation occurs early in acute mild and severe pancreatitis and whether the intestinal expression of tight junction proteins (claudins-2, -3, -4, -5, -7), apoptosis or proliferation would explain the possible translocation. Methodology: Fifteen pigs were randomized to controls (n=5) or to develop mild edematous pancreatitis (n=5, saline infusion to pancreatic duct) or severe necrotic pancreatitis (n=5, taurocholic acid infusion). Translocation was studied by measuring bacterial cultures from portal vein blood and mesenteric lymph nodes. Immunohistochemical expression of the tight junction proteins, apoptosis rate (TUNEL) and Ki-67 were analyzed quantitatively from the epithelium of the jejunum and colon. Results: There was no bacterial translocation during the 6 hours followup, nor changes in the expression of tight junction proteins claudins-2 and -5 in jejunum or colon. Saturation and proportional area of claudin-3 staining decreased in the colon, as did claudins-4 and -7 staining in the jejunum of the necrotic pancreatitis group. Increased apoptosis was found in all samples from controls and the edematous pancreatitis group but not in jejunum in the necrotic pancreatitis group. Ki-67 activity tended to increase in the upper half of the villus in edematous and necrotic pancreatitis. There were no changes in the basic histology. Conclusions: The major finding of this study was that bacterial translocation from the gut is not present at the beginning of acute pancreatitis. Tight junction proteins claudin-2 and -5 do not become altered in the early stages of pancreatitis. Claudin-3 decreases in the colon and claudins-4 and -7 in the jejunum in necrotic pancreatitis. Laparotomy itself causes increased apoptosis in the colon and the jejunum.     

Comparison of different methods for detecting glaucomatous visual field progression

PURPOSE: To compare the performance characteristics of seven methods for analyzing glaucomatous visual field progression, using a combination of real patient data and computer simulation techniques. METHODS: The initial and final visual field results, separated by 7 years and measured with the full-threshold 30-2 program of the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA) of 76 patients with open-angle glaucoma were used. A computer simulation program generated 14 interim semiannual visual fields under conditions of high, moderate, and no variability. Progression was analyzed using the methods of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), three criteria based on the Glaucoma Change Probability (GCP) analysis, and two criteria based on point-wise linear regression analysis (PLRA). Specificities were calculated by using the same visual field of each patient as both the initial and final field (no progression) under conditions of moderate and high variability. RESULTS: Under the no-variability condition, progression rates were 18% for the AGIS, 36% for CIGTS, 47% to 62% for the three GCP methods, and 72% and 84% for the two PLRA methods. Progression rates increased with greater variability with the three GCP methods and decreased with all other methods. The time to detect confirmed progression was longest for the PLRA methods and shortest for the CIGTS and GCP methods. Under the moderate-variability condition, all methods yielded high specificity. The AGIS, CIGTS, and one of the GCP and PLRA methods were relatively resistant to high variability and maintained high specificities. CONCLUSIONS: The AGIS and CIGTS methods had high specificity, but classified fewer cases of progression than the other methods. The GCP methods determined progression earliest; however, they were generally not as specific. Methods based on PLRA were specific but times to confirmed progression were the longest.     

High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer

Comparative genomic hybridization (CGH) studies have provided a wealth of information on common copy number aberrations in pancreatic cancer, but the genes affected by these aberrations are largely unknown. To identify putative amplification target genes in pancreatic cancer, we performed a parallel copy number and expression survey in 13 pancreatic cancer cell lines using a 12,232-clone cDNA microarray, providing an average resolution of 300 kb throughout the human genome. CGH on cDNA microarray allowed highly accurate mapping of copy number increases and resulted in identification of 24 independent amplicons, ranging in size from 130 kb to 11 Mb. Statistical evaluation of gene copy number and expression data across all 13 cell lines revealed a set of 105 genes whose elevated expression levels were directly attributable to increased copy number. These included genes previously reported to be amplified in cancer as well as several novel targets for copy number alterations, such as p21-activated kinase 4 (PAK4), which was previously shown to be involved in cell migration, cell adhesion, and anchorage-independent growth. In conclusion, our results implicate a set of 105 genes that is likely to be actively involved in the development and progression of pancreatic cancer.     

Methodology for restoring functional leg length in revision total hip arthroplasty

Functional leg length was measured in 30 patients before and after revision total hip arthroplasty. The authors emphasize the importance of preoperative planning, and determination of adjustment of the leg length should be aimed at a balanced attitude of the entire pelvis and lower back. In order to correct the length inequality, the leg was lengthened in the revision in 25 cases, left unchanged in 2 cases, and shortened in 3 cases. The mean functional leg-length inequality was 13 mm before operation and 4 mm after operation. The mean radiographic inequality between the upper surfaces of the iliac crest was 13 mm before operation and 9 mm after operation. The side operated was more often functionally shorter than the other side before operation, and longer than the other side after operation. The authors emphasize the importance of functional leg length in revision hip arthroplasty. The functional length discrepancy can be corrected in revision, but there appears to be a risk of overlengthening.     

Family dynamics in families of severe COPD patients

Aim and objectives. The purpose of this study was to describe family dynamics in families with severe chronic obstructive pulmonary disease (COPD) on the basis of Barnhill's framework for healthy family systems. The sample consisted of 35 severe COPD patients and 30 family members at Tampere University Hospital, Finland or in the neighbouring regions. Background. Chronic obstructive pulmonary disease is a public health problem worldwide. It is a slowly progressive airway disease, producing a decline in lung function which is not fully reversible. Design. The sample included the families of patients without oxygen therapy and the families of patients who had long-term oxygen therapy (LTOT). The data were collected using the Family Dynamics Measure 2 (FDM2) and the Family Dynamics Questionnaire (FDQ). Method. A quantitative research method was employed in the study. Frequency and percentage distributions, as well as cross-tabulations, were used to describe the data. Mean values and standard deviations were calculated for the sum variables of six dimensions of the FDM2. Results. In the dimensions of individuation, mutuality and flexibility, dynamics in the families of patients with LTOT was significantly better than of the patients without oxygen therapy. Especially in the dimension of mutuality, the families of LTOT patients functioned very well, while in the dimensions of communication and roles, family dynamics in these families was notably worse, although still good. Conclusion. Poor self-identity – enmeshment, isolation from others and lack of flexibility to varying conditions – in families with severe COPD can weaken the ability of the families to manage in everyday life. Relevance to clinical practice. Families need family nursing to adapt to alterations occurring when a family member has severe COPD. Nurses can give support and help for these families for their roles of patient and caregiver, as well as opportunities to speak with someone about their situation.     

Valproate in the treatment of epilepsy in girls and women of childbearing potential

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.     

Analyses of Gingival Adhesion Molecules in Periodontitis: Theoretical In Silico,Comparative In Vivo,and Explanatory In Vitro Models

Background: A deeper understanding of periodontitis pathophysiology is central to future development of novel biomarkers and therapeutics. The following is reported here: 1) an in silico network model of interactions among cell adhesion molecules and a network‐focused microarray analysis of the corresponding genes in periodontitis; 2) analysis of secretions of adhesion molecules in gingival tissue samples from patients with periodontitis and healthy controls; and 3) effect of the human neutrophilic peptide‐1 (HNP‐1) on epithelial adhesion molecules. Methods: The network model identified 85 nodes in relation to the interactions of adhesion molecules. Subsequently, the relative gene expression was overlaid on the network model. Differential gene expression was analyzed, and false discovery rate control was performed for statistical assessment of the microarray data. Both tissue and cell culture samples were immunostained for desmocollin (DSC)2, occludin (OCLN), desmoglein (DSG)1, tight junction protein 2, and gap junction protein α. Results: The differential gene expression analysis revealed that the epithelial adhesion molecules were significantly lower in abundance in individuals with periodontitis than controls. In contrast, the genes for leukocyte adhesion molecules showed a significant upregulation. Immunostainings revealed elevated secretions of both DSG1 and OCLN in periodontitis. An in vitro model suggested reduced DSC2 and OCLN secretions in the presence of HNP‐1. Conclusions: Gene expression of gingival adhesion molecules in periodontitis is regulated by leukocyte transmigration, whereas the neutrophilic antimicrobial peptide HNP‐1 is noted as a putative regulator of epithelial adhesion molecules. These observations contribute to the key mechanisms by which future biomarkers might be developed for periodontitis.     

Tension‐free vaginal tape procedure without preoperative urodynamic examination: Long‐term outcome

Objectives: To evaluate the long‐term outcome of the tension‐free vaginal tape procedure. Methods: A total of 191 patients were operated on with tension‐free vaginal tape between January 1998 and May 2000. Of these, 127 (66%) had stress urinary incontinence, 64 (34%) had mixed urinary incontinence and 39 (20%) had recurrent incontinence. A total of 34 (18%) patients had had concomitant surgery. The diagnosis of incontinence was based on a history of leakage during stress and physical examination with a supine stress test in all patients. Tension‐free vaginal tape was carried out under local (82%) or spinal (18%) anesthesia. After a mean of 10.5 years follow up, the assessment included a gynecological examination and a supine stress test. Subjective outcome was evaluated with Urinary Incontinence Severity Score, Detrusor Instability Score, visual analog scale, European quality of life‐five dimensions, European quality of life – visual analog scale and short versions of Incontinence Impact Questionnaire‐7 and Urogenital Distress Inventory‐6. Objective cure was defined as a negative stress test and an absence of reoperation for incontinence during the follow up. Results: A total of 138 (72%) of 191 patients were evaluated. Patients with minimally invasive surgery before operation had significantly higher scores in Urinary Incontinence Severity Score, Detrusor Instability Score, Incontinence Impact Questionnaire‐7 and Urogenital Distress Inventory‐6 at follow up than the patients with stress urinary incontinence (P < 0.01). Recurrent incontinence and concomitant surgery did not affect the long‐term outcome. Three patients (2.3%) had late‐onset adverse events. The objective and subjective cure rates were 90% and 78%, respectively. Conclusions: The tension‐free vaginal tape procedure is effective and safe even after 10 years. The objective cure rate is high, but the subjective outcome is significantly lower in mixed urinary incontinence patients compared with patients with pure stress urinary incontinence. Recurrent stress urinary incontinence does not affect the outcome, and tape‐related problems are rare.