Integrin alpha4beta1/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma cells to hepatic sinusoidal endothelial cells under flow.

Adhesion and stabilization of circulating tumor cells to endothelial cells in target blood vessels play an important role in the complex process of metastasis. We examined the cell surface receptors involved in the liver-metastatic adhesive interactions of murine RAW117 large-cell lymphoma cells to unstimulated hepatic sinusoidal endothelial cells (HSE) under physiological flow conditions. Flow cytometric analysis indicated that VCAM-1, ICAM-1 and PECAM-1 are constitutively expressed on the surfaces of both HSE and RAW117 cells. However, monoclonal antibody (mAb) blockade studies showed that ICAM-1 and PECAM-1 affected neither the attachment nor the stabilization step of the adhesion of RAW117 cells to HSE cell monolayers under flow. In contrast, RAW117 cells required a significantly lower shear stress to establish adhesion to HSE cells when VCAM-1 receptors on HSE cells were blocked with mAb. Furthermore, the presence of the anti-VCAM-1 mAb significantly decreased the extent of adhesion compared to that of the control, without affecting adherent cell stabilization times. Blocking the alpha4 integrin subunits present mainly on RAW117 cells produced similar results to those previously observed with anti-VCAM-1 mAb. Although constitutively present mainly on the surfaces of RAW117 cells, MAdCAM-1 and beta7 integrin subunit do not appear to play a role in either the arrest or stabilization of RAW117 cells on HSE cell monolayers. However, blocking the beta1 integrin subunit on the RAW117-H10 cells reduced adhesion to the same extent as anti-alpha4 and anti-VCAM-1 treatments. These observations suggest that an interaction of integrin alpha4/beta1 on RAW117 cells with liver endothelial VCAM-1 occurs during the early stages of the adhesion process and may be important in liver metastasis.

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Clinical evaluation of the urinary sediment after renal allotransplantation.

The detection of lymphoid cells by routine examination of the urine after renal allotransplantation has proved to be a useful early indication of rejection. In a study of 36 rejection episodes, 20 (56%) were associated with a significant number of lymphocytes in the urine. The incidence was much higher when rejection occurred during the first month after operation (76%); lymphocytes were rarely found when rejection occurred after three months. The appearance of lymphocytes in the urine was of particular value for detecting rejection in patients with prolonged oliguria after transplantation.

The effect of membrane permeability on ESRD: design of a prospective randomised multicentre trial.

The different permeability of high-flux and low-flux dialysis membranes results in different removal capacity, particularly for uremic toxins of middle and large molecular weight. High-flux dialysers have been evaluated in clinical and epidemiological studies for their effect on mortality, morbidity, dialysis-related amyloidosis, nutritional status, response to erythropoietin treatment, dialysis tolerance and the preservation of residual renal function. Many of these studies, however, lack a prospective design and randomised treatment allocation, or have too few patients and too short a follow-up. Therefore, this clinical trial was designed to prospectively investigate the long-term effect of membrane permeability on clinical outcome in a larger number of patients. The primary objective is to compare the effect of membrane permeability on mortality of patients on bicarbonate hemodialysis and treated with a minimum dialysis dose. Patients included in the study should have been on hemodialysis for no longer than one month and have serum albumin 4 g/dl or lower. Patients will be randomised to either the experimental or the control group. During the four-week run-in period the treatment parameters will be established in order to achieve the required dialysis dose. During the maintenance period of three to five years regular visits are scheduled to record clinical and laboratory parameters, to measure Kt/V and to adapt the treatment parameters. Altogether a minimum of 660 patients should be enrolled within a two-year recruitment period.

Prosthetic mesh repair of multiple recurrent and large abdominal hernias in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to find out whether prosthetic mesh repair of recurrent and large abdominal hernias in continuous ambulatory peritoneal dialysis (CAPD) patients is effective in maintaining them on CAPD. DESIGN: Retrospective analysis of case notes over a period of 5 years. SETTING: Single renal unit of a university hospital. PATIENTS: Forty-six of 217 CAPD patients (16%) had their hernias repaired. Among them, 5 women in whom hemodialysis was not possible had multiple or large hernias repaired with polypropylene (PP) mesh. RESULTS: Radical repair was achieved by a modified operation consisting of a conventional hernioplasty complemented by a supporting prostetic overlay mesh, without discontinuation of CAPD. The patients continued CAPD for a mean period of 17.6 months without hernia recurrence. Two patients died in the twelfth and fifteenth post-operative month due to cardiac arrest and hepatic failure, respectively, and the remaining 3 are alive and have been doing well on CAPD for 13, 14, and 21 months. CONCLUSIONS: Prosthetic mesh repair of large recurrent hernias in CAPD patients with vascular access problems seems to be a valuable method to maintain them on this renal replacement therapy.

Emotional support of cancer patients: the nursing approach.

The present study attempts to classify cancer patients' psychologic responses in order of importance, and to identify the role of the oncology nursing staff in the moral support of these patients. We want to emphasize the significant role of the nursing staff because until 1990, Greece had no specialization in the field of oncology nursing. After the initial diagnosis of cancer, the patient was considered as emotionally depressed. Our sample consisted of 120 cancer patients from the southwestern regions of Greece. From our research, we concluded that the factors generally characterizing cancer patients, in order of priority, are (a) moral support from family and friends (p < 0.0001), (b) psychologic reactions after some months (p < 0.0001), (c) sex (p = 0.0006), (d) age (p < 0.0001), (e) marital status (p < 0.0001), and (f) psychologic reactions during the first days following diagnosis (p = 0.018) because of the shock experienced. More specifically, we wish to stress the absence of the consulting role on the part of the nursing staff. This finding is worth the keen attention of consultants on health matters. Nurses have a great deal to contribute to the emotional care of cancer patients, and are puzzled about the reasons why they are not asked to participate in this important function.

Urinary tract infections after renal transplantation.

From 1980 to 1983, 69 patients (36 male) with end-stage renal disease underwent kidney transplantation (11 from cadaveric donors). Twenty-six out of 69 (17 male) with a mean age of 37 years (range 16-50 years) developed 69 UTI episodes. The standard immunosuppressive regimen consisted of prednisolone and azathioprine and, in selected cases, antilymphocyte globulin or cyclosporin A were given for a short period of time. Thirty-five episodes (50%) occurred within two months of the operation. The most commonly isolated bacteria were E. coli (28 cases), Ps. aeruginosa (16) and Proteus mirabilis (9). Kidney graft dysfunction, diabetes mellitus, urological complications and antirejection treatment were the main predisposal factors. Recurrence or reinfections were finally diagnosed in 19/26 patients (73%). Thirteen patients presented with asymptomatic bacteriuria (55% of episodes). Aminoglycosides, ureidopenicillins and third-generation cephalosporins were found to be very effective for treating severely ill, febrile patients. In addition, trimethoprim/sulphamethoxazole and mecillinam were useful for patients on long-term chemotherapy. There were no deaths or impairment of the renal graft function directly attributable to the urinary infection. In conclusion, UTIs are a very common cause of morbidity in kidney graft recipients, with the highest incidence in the early post-transplant period. Recurrences or reinfections occur often and asymptomatic bacteriuria is a common finding which needs not be treated aggressively in the absence of symptoms or obstructive uropathy. Patient and graft survival in the long term remain unaffected by the presence of the urinary infection.

Plasma exchange (PE) treatment in drug-induced toxic epidermal necrolysis (TEN).

Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare fulminating skin disease notorious for its rapidly progressive course and high mortality rate. TEN is characterized by the sudden onset of epithelial necrosis of skin with frequently associated involvement of the gastrointestinal, genitourinary tract and bronchopulmonary linings. We describe the clinical course of five patients with severe drug-induced TEN, treated with PE. The suspected drugs were carbamazepine in one patient, paracetamol in one, a combination of paracetamol and mefenamic acid in one, allopurinol in one and ciprofloxacin in one. Three had a skin involvement affecting almost the entire surface of the body. In addition to the skin lesions, mouth, esophagus and lungs were also involved. Steroids proved ineffective. PE was carried out because of the rapid deterioration of the clinical picture. The mean number of PE sessions was 3.22 (range 1-5). Complete remission of the syndrome was achieved in four patients. One patient died due to septic shock. As so far there is no treatment of proven value for this condition, controlled trials should be set up in order to assess the value of PE in TEN.

Ciprofloxacin in critically ill children.

Data regarding the use of fluoroquinolones in critically ill children are scarce. We present our experience regarding the use of ciprofloxacin in this specific patient population. We prospectively identified all paediatric patients who received ciprofloxacin treatment in the intensive care unit of the tertiary care P. & A. Kyriakou Children's Hospital during a three year period (2005 to 2008). Eighteen paediatric patients (mean age 23 months, 12 females) who received intravenous ciprofloxacin were identified. Various underlying diseases, including malignancy and immunodeficiency, were observed. None of the evaluated patients had cystic fibrosis. Fourteen patients had bacteraemia (mainly caused from Gram-negative pathogens), one had Stenotrophomonas maltophilia pneumonia, while no pathogen was identified in three patients. The latter patients received ciprofloxacin due to the severity of their clinical manifestations. All patients with microbiologically documented infections recovered. Three deaths attributed to the underlying diseases were noted. Within a 10-day follow-up, two cases of diarrhoea, one case of vomiting and one case of reversible supraventricular tachycardia were noted. No case of QT prolongation was noted. The short-term follow-up hampered any assessment of joint and cartilage toxicity, potentially associated with ciprofloxacin treatment. Our study suggests that ciprofloxacin may be a useful option for critically ill children without cystic fibrosis. Even though firm conclusions regarding the safety profile of ciprofloxacin in critically ill children could not be drawn, our study provides useful information regarding short-term adverse events associated with ciprofloxacin.