Peritoneal T cell responses can be polarized toward Th1 or Th2 in children on chronic peritoneal dialysis

Peritoneal T cell responses can be polarized toward Th1 or Th2 in children on chronic peritoneal dialysis. Previous studies on the peritoneal immune system described the presence of activated T lymphocytes in peritoneal effluents from subjects on chronic peritoneal dialysis (CPD). Since Th1/Th2 polarized response can influence the outcome of specific infectious diseases, we investigated if activated Th1/Th2 cells can be detected in peritoneal effluents during peritoneal dialysis, in order to better understand the role of T cells in the mechanisms of peritoneal defense. We have studied 8 children (4 males, 4 females, mean age 5.8 +/- 5.7 years, range 0.3-13.4) on CPD. Peritoneal cells have been isolated from peritoneal effluents by centrifugation. Immunofluorescent staining of intracellular cytokines for flow cytometric analysis was used to detect the percentage of T cells producing either IFN-gamma (Th1) or IL-4 (Th2). In the initial study 3 months after CPD initiation, high percentages of IFN-gamma positive peritoneal T cells (38% and 63%) were detected in two subjects; this finding is consistent with a Th1 polarization of peritoneal T cells. In another subject, high percentages of IL-4 positive T cells (31%) were detected, suggesting a Th2 polarization of peritoneal T cell response. Small amounts of either Th1 or Th2 T cells (2-4%) were also detected in the other subjects. At the 1 year follow-up, Th1 polarization persisted in one subject (18% IFN-gamma positive peritoneal T cells), in another a shift from Th1 to Th2 was observed, and in the other subject a down regulation of both T cell subsets occurred. The finding that a predominance of T cells producing either IFN-gamma or IL-4 was found in 3 out of 8 children strongly suggests that peritoneal T cell responses can be polarized toward Th1 or Th2. The decrease of Th1 and/or Th2 polarized T cells in the peritoneum of 4 out of 6 subjects (after 1 year) suggests that CPD can play an immunosuppressive role on T cell peritoneal responses. Further studies are needed in order to define whether different T helper activation patterns are associated with a higher risk of peritoneal infection or of peritoneal damage.     

Adequacy of dialysis in children: does small solute clearance really matter?

Measurement of dialysis adequacy relies on an assessment of small molecule clearance during the dialysis procedure. However, recent adult studies (HEMO and ADEMEX) that pushed clearance to maximally achievable levels within practical constraints of thrice-weekly hemodialysis or four times daily continuous ambulatory peritoneal dialysis failed to demonstrate improvements in patient outcome above current guidelines. The relatively low incidence of pediatric compared with adult end-stage renal disease limits large-scale study of pediatric dialysis. Several single-center pediatric studies demonstrate a lack of association between small solute clearance alone and patient growth. The aim of the current article is to review the relevant pediatric and adult studies of small solute clearance and put them in the context of optimal dialysis provision. While small solute clearances do indeed matter, clearance is not all that matters. Our quest to provide optimal dialysis requires that we also focus our attention on patient nutritional status, increased dialysis delivery (daily/nocturnal hemodialysis), and adjunctive dialysis modalities (hemofiltration and renal tubular replacement therapy).     

Mycobacterial peritonitis in pediatric peritoneal dialysis patients

Peritonitis is the most common complication and the leading cause of death in pediatric peritoneal dialysis (PD) patients. According to the most recent data available from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), approximately 25% of pediatric PD patients who die succumb to infection. There are no reported cases of Mycobacterium tuberculosis (MTB) or Mycobacterium avium-intracellulare peritonitis in the NAPRTCS registry. With an increasing incidence of MTB worldwide and the impairment of cellular immunity in chronic renal failure patients, it is not surprising that mycobacterium peritonitis can occur in PD patients. We report two pediatric PD patients with mycobacterial peritoneal infection diagnosed over an 11-year period at our institution. One patient presented with a malfunctioning Tenckhoff catheter and again 3 years later with hyponatremia and ascites. The other presented with recurrent culture-negative peritonitis. These cases illustrate the importance of more extensive evaluation of PD complications, to include evaluation for mycobacterium with special media or peritoneal biopsy, in the above clinical settings if the routine work-up is unrevealing.     

Survival and Recurrence After a Sphincter-Saving Resection and Abdominoperineal Resection for Adenocarcinoma of the Rectum At or Below the Peritoneal Reflection: A Multivariate Analysis

Purpose. The purpose of this study was to determine whether the type of operation [sphincter-saving resection (SSR) or abdominoperineal resection (APR)] for primary adenocarcinoma of the rectum at or below the peritoneal reflection affects survival and recurrence after curative surgery. Methods. This retrospective study included 184 patients who underwent curative surgery achieved by the following two types of operation between 1989 and 1998: (1) SSR (n = 116 patients) including a low anterior resection with either double-stapling technique (n = 86) or transanal coloanal anastomosis (n = 30); (2) APR (n = 91). The outcome factors evaluated were survival and tumor recurrence. Both univariate and corrected (multivariate Coxs and logistic regression) analyses were used to evaluate the data. The median follow-up was 47.4 months for patients alive at study conclusion. Results. Disease-free and disease-specific survivals, and the frequency and location of recurrence after surgery did not differ between the two types of operations. Multivariate analyses showed that the type of operation was not a significant independent variable in predicting disease-free survival or in the development of both local and distant recurrences after surgery. In addition, tumor-related factors (stage or histologic grade) were significant predictors of the outcome after surgery. Conclusions. The type of operation (SSR or APR) did not affect the survival or recurrence after a curative resection for adenocarcinoma of the rectum at or below the peritoneal reflection.     

Repeated resection for extrahepatic recurrences after hepatectomy for ruptured hepatocellular carcinoma

In March 1999, a 54-year-old man with chronic hepatitis C was referred to our hospital because of ruptured hepatocellular carcinoma (HCC) located in Couinauds segments 4 and 8. He underwent central bisegmentectomy of the liver with partial resection of the diaphragm. After the first surgery, extrahepatic metastases were found on different occasions in the abdominal wall, thoracic cavity, and greater omentum and were all surgically resected. In February 2001, the serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level increased markedly to 19000mAU/l. Magnetic resonance imaging showed a massive right subphrenic tumor with invasion to the right diaphragm and posterior segment of the liver. The patient underwent en bloc resection of the tumor, diaphragm, posterior segment of the liver, and right lower pulmonary lobe. After the surgery, the PIVKA-II level rapidly decreased, and it has remained within the normal range to date. Two years after the last surgery, the patient is doing well without any extrahepatic recurrence, although small intrahepatic recurrences have been completely treated by radiofrequency ablation and transcatheter arterial chemoembolization. Ruptured HCC often exacerbates the risk of peritoneal dissemination and is usually difficult to completely resect. This is an extremely rare case of a patient who successfully underwent five repeated resections for extrahepatic recurrences after hepatectomy for ruptured HCC.     

Periodic limb movement disorder and restless legs syndrome in dialysis patients

BACKGROUND: Sleep disturbances, in particular restless legs or limb movements, during the night are often reported by uremic patients. However, polysomnography (PSG) studies have never been carried out to confirm the actual occurrence of these disorders and the association with other objective and self-reported sleep-wake data. METHODS: Forty-eight participants were subjected to a 2-day PSG. These data on sleep including periodic limb movements, which are associated with restless legs, were correlated with clinical observations, quality of sleep-wake and life questionnaires, and with biochemical and neurographical measures. RESULTS: Restless legs syndrome (RLS) was observed in 58.3% of the patients and periodic limb movement disorder (PLMD) occurred in 70.8% of the patients. PLMD was revealed polysomnographically in almost 90% of the RLS patients. Patients with both PLMD and RLS had significantly poorer sleep quality than those with neither disorder or with PLMD alone, both in terms of self-reported data and the PSG. Quality of life was significantly worse in patients with RLS and PLMD compared to those patients with neither disorder. PLMD patients also tended to have a lower quality of life. All other metabolic measures and the results of a nerve conduction test were not correlated with RLS and/or PLMD. CONCLUSION: There was a high prevalence of severe RLS and PLMD in the present sample of uraemia patients. Nearly all RLS patients had severe PLMD. RLS (in combination with PLMD) in dialysis is associated with poor sleep quality, insomnia complaints, depression and emotional distress. Our results suggest that PLMD per se is also clinically relevant.     

Simultaneous multiple tendon ruptures complicating a seizure in a haemodialysis patient

Non-traumatic rupture of large tendons is identified as a contributor to morbidity in patients who receive haemodialysis. The injury is likely to become more common as the duration of survival on dialysis extends. A number of predisposing factors leading to tendon injury have been identified in the literature, including secondary hyperparathyroidism, beta(2)-microglobulin associated amyloidosis, corticosteroid treatment and fluoroquinolone antibiotic use. This is a case report of a 31-year-old male who presented with simultaneous large tendon ruptures following epileptiform seizures. These occurred after 10 years of treatment for end-stage renal failure, including haemodialysis, with progressive secondary hyperparathyroidism. A review of the literature confirms progressive hyperparathyroidism as an important risk factor for large tendon rupture in patients on haemodialysis.     

Prevalence of Helicobacter pylori antibodies in long-term dialysis patients

Background: Helicobacter pylori has been reported to play an important role in the development of gastritis and gastric ulcer. Methods: This study included 168 patients with end‐stage renal disease (ESRD; 30 non‐dialysis patients, 138 patients receiving dialysis; mean duration of dialysis: 57.3 ± 61.7 months) and 138 control volunteers. We investigated the prevalence of H. pylori infection by measuring H. pylori antibody (IgG) levels. Results: The prevalence of H. pylori infection was 62.3% in the control group, 53.3% in the non‐dialysis patients, and 36.9% in the dialysis patients. The percentage decreased with a reduction of renal function. In addition, the proportion of H. pylori‐positive patients decreased with the duration of dialysis, and the antibody titre was also significantly decreased. There was no association between long‐term oral administration of H2RA (H2 receptor antagonist) and the incidence of H. pylori infection. Conclusion: Among dialysis patients, the proportion of H. pylori‐positive patients was low. An aetiological factor other than H2RA agents was suggested. Renal failure or dialysis treatment may influence H. pylori infection.     

Endometrial and peritoneal macrophages: expression of activation and adhesion molecules

PROBLEM: Macrophages are highly individualized in tissues and their activities are a reflection of systemic and local environmental signals. The expression of activation (CD69, CD71) and adhesion (CD54) molecules on the surface of CD14+ endometrial macrophages at various phases of the menstrual cycle was compared with the cell surface receptors of peritoneal fluid macrophages. METHOD OF STUDY: Two-colour-flow cytometry was used to determine the peritoneal and endometrial macrophage phenotype. RESULTS: Endometrium macrophages expressed a lower level of CD69+ and CD54+ macrophages than peritoneal macrophages. However, CD71 receptors displayed similar expression in both macrophage populations, endometrium and peritoneal, except during the proliferative phase. CONCLUSION: These findings demonstrate the differences between macrophages from endometrium and peritoneal fluid with regard to CD69, CD71 and CD54 expression. In addition, increased numbers of endometrial macrophages in the late secretory phase of the menstrual cycle suggest that they may play a role in menstruation.     

Liposome/water lipophilicity: methods, information content, and pharmaceutical applications

This review discusses liposome/water lipophilicity in terms of the structure of liposomes, experimental methods, and information content. In a first part, the structural properties of the hydrophobic core and polar surface of liposomes are examined in the light of potential interactions with solute molecules. Particular emphasis is placed on the physicochemical properties of polar headgroups of lipids in liposomes. A second part is dedicated to three useful methods to study liposome/water partitioning, namely potentiometry, equilibrium dialysis, and (1)H-NMR relaxation rates. In each case, the principle and limitations of the method are discussed. The next part presents the structural information encoded in liposome/water lipophilicity, in other words the solutes' structural and physicochemical properties that determine their behavior and hence their partitioning in such systems. This presentation is based on a comparison between isotropic (i.e., solvent/water) and anisotropic (e.g., liposome/water) systems. An important factor to be considered is whether the anisotropic lipid phase is ionized or not. Three examples taken from the authors' laboratories are discussed to illustrate the factors or combinations thereof that govern liposome/water lipophilicity, namely (a) hydrophobic interactions alone, (b) hydrophobic and polar interactions, and (c) conformational effects plus hydrophobic and ionic interactions. The next part presents two studies taken from the field of QSAR to exemplify the use of liposome/water lipophilicity in structure-disposition and structure-activity relationships. In the conclusion, we summarize the interests and limitations of this technology and point to promising developments.