Clinical expression and course in patients with late onset systemic lupus erythematosus.

BACKGROUND: To analyze the pattern of clinical expression and the 5-year disease course in Caucasian patients with late onset of systemic lupus erythematosus (SLE) and to compare the findings with an early onset SLE group. METHODS: Medical records of 551 patients who presented with SLE at hospitals of the region of Thessaloniki between 1989 and 2007 were studied. Patients who developed SLE at or after the age of 50 years were classified as the late onset group, while younger patients served as the early onset group. Data on clinical manifestations and damage accrual at disease onset and at 5 years was obtained and compared between the two groups. RESULTS: In 121 patients, the disease started after the age of 50 years. Elderly patients showed less pronounced female predominance and less often presented with malar rash, nephropathy, fever and lymphadenopathy, while lung involvement, pericarditis and sicca syndrome were more frequent. Damage accrual was similar in both groups. The main causes of damage at 5 years differed, with the elderly exhibiting more cardiovascular damage. They also had a higher incidence of hypertension and osteoporosis at 5 years. CONCLUSIONS: Caucasian SLE patients with late onset of the disease present with different clinical manifestations, suggesting that age affects the expression of SLE. Damage accrual at 5 years is similar in the elderly and the younger patients. However, the causes of this damage and the occurrence of other comorbidities follow a different pattern, possibly reflecting the disease process and the effects of aging.

Clinical expression and morbidity of systemic lupus erythematosus during a post-diagnostic 5-year follow-up: a male:female comparison.

The aim of this study was to analyse the prevalence of the most relevant clinical features of the diagnosis of systemic lupus erythematosus (SLE) in a sample of male patients with lupus as well as the incidence of the main causes of morbidity in a 5-year period after the diagnosis. A further aim of this study was to investigate the impact of gender on expression and morbidity of SLE. Data were collected from the medical records of 59 male and 535 female patients with SLE who were diagnosed at the hospitals in the region of Thessaloniki. Several differences in the expression and morbidity of the disease were found in relation to the gender of the patient. Male patients had a higher prevalence of thromboses, nephropathy, strokes, gastrointestinal tract symptoms and antiphospholipid syndrome when compared with female patients, but tended to present less often with arthralgia, hair loss, Raynaud's phenomenon and photosensitivity as the initial clinical manifestations. During the 5-year follow-up, positive associations have been found between male gender and the incidence of tendonitis, myositis, nephropathy and infections, particularly of the respiratory tract. In conclusion, this study has provided information regarding the features of clinical expression and morbidity in male patients, and has shown that gender is a possible factor that can influence the clinical expression of SLE.

Phosphorus control in peritoneal dialysis patients.

Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and mean duration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3+/-0.65, weekly creatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of <400 ml day(-1). Mean serum phosphorus level was 4.9+/-1.3 mg per 100 ml, serum Ca(2+) 9.4+/-1.07 mg per 100 ml, iPTH 267+/-356 pg ml(-1), ionized Ca(2+) 1.08+/-0.32 mg per 100 ml, calcium phosphorus (Ca x P) product 39+/-19 mg(2)dl(-2), 25(OH)D(3) 8.3+/-9.3 ng ml(-1), 1,25(OH)(2)D(3) 9.7+/-6.7 pg ml(-1), total alkaline phosphatase 170+/-178 U l(-1), and bone alkaline phosphatase 71+/-108 U l(-1). While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca(2+) level was > or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136 patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P<0.027) and iPTH (P=0.001), and negatively correlated with age (P<0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (>65 years) compared to younger patients; mean levels were 5.1+/-1.4 and 4.5+/-1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca x P in 73%, serum Ca(2+) in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosphorus control in the majority of patients.

Cost-effectiveness of losartan in diabetic nephropathy: a Greek perspective.

BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease (ESRD), which involves substantial economic burden. The primary objective of this study was to estimate the potential effect of losartan on the costs associated with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary aim was to approximate the direct health care cost of renal replacement therapy (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical data were derived from the RENAAL study. All costs were calculated from the perspective of the Greek social insurance system, in 2003 euros. Future costs were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity analyses were performed. RESULTS: The reduction in the number of ESRD days over 3.5 years in patients treated with losartan reduced ESRD-related costs by 3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net cost savings increase thereafter, increasing to 2,686.48 euros per patient over a period of 4.0 years. The results were robust under a wide range of plausible assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per patient. The total economic burden of RRT for the year 2003 has been estimated at 304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of patients with diabetic nephropathy in Greece with losartan is cost-effective, as it leads to important savings for the social insurance system by slowing the progression to ESRD.

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

UNLABELLED: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Randomized studies have shown that postoperative chemotherapy with or without radiation therapy (RT) improved local control and survival of patients with stages II or III rectal cancer. However, the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined. Modulation of fluorouracil (FU) by leucovorin (LV) has yielded a highly significant difference in response rate from that of FU monotherapy, as suggested by an overview of randomized trials in patients with advanced colorectal cancer. However, this difference in response rate did not translate into a survival benefit. PURPOSE: To evaluate the impact on the disease-free survival (DFS) and overall survival (OS) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU administration alone or with additional chemotherapy using FU and high-dose LV. PATIENTS AND METHODS: From October 1989 until February 1997, 220 patients were randomized postoperatively to receive either one cycle of chemotherapy with FU (600 mg/m2/week x 6 followed by a two-week rest) and leucovorin (LV, 500 mg/m2/week x 6 as a two-hour infusion) followed by pelvic RT with concomitant FU (400 mg/m2) as a rapid intravenous injection during the first three and last three days of RT, and three more cycles of the same chemotherapy with FU and LV (standard, group A, 111 patients) or pelvic RT with concomitant FU only (experimental, group B, 109 patients). RESULTS: As of August 1998, after a median follow-up of 4.9 years, there was no significant difference in either three-year DFS (Group A, 70.3%; group B, 68.2%, P = 0.53) or OS (group A, 77%; group B, 73.3%. P = 0.75). Cox multivariate analysis revealed stage of disease, number of infiltrated nodes, tumor grade, presence of regional implants and perforation to be significant prognostic factors. The incidence of severe side effects was significantly higher in the patients in group A than in those in group B (32.4% vs. 4.6%, P < 0.0001). CONCLUSIONS: The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10% three-year survival benefit over that of concomitant RT and bolus infusion of FU, and significantly increases toxicity in patients with stages II or III rectal cancer.

Survival and complications of 225 catheters used in continuous ambulatory peritoneal dialysis: one-center experience in Northern Greece.

This study reports our experience with permanent peritoneal catheters. From July 1983 until December 1997, 225 catheters were implanted surgically in 207 patients (120 males, 87 females) with mean age of 58+/-16 years (range: 2-82 years), and a mean duration of continuous peritoneal dialysis (CAPD) of 21.9+/-21.3 months (range: 1-145 months). Two hundred and seventeen catheters were used in 199 patients suffering from end-stage renal disease (ESRD), and 8 catheters in 8 patients with end-stage heart failure resistant to medical therapy. One patient used 3 catheters and 16 patients used 2 catheters. The catheters used were: Tenckhoff, 2; Oreopoulos-Zellerman-1 (OZ-1), 10; OZ-2, 205; and OZ-pediatric, 8. All catheters were implanted by the same surgical team, through a paramedian incision under local anesthesia. By life table analysis, the actuarial survival rates at 1 year, 2 years, 3 years, and 5 years were 97%, 92%, 87%, and 82% respectively for all catheters. The catheter-related complications were: 5 obstructions, 2 dislodgments, 13 dialysate leaks (6 early; 7 late), 90 exit-site/tunnel infections (in 56 patients), 2 cuff extrusions, and 37 hernias (in 31 patients). Eighteen catheters were replaced for persistent peritonitis (15 cases), dislodgment (1 case), obstruction (1 case), and accidental shortening (1 case). The total observation period was 4526 patient-months. The overall incidence of peritonitis was one episode per 15 patient-months, and of exit-site/tunnel infections was one episode per 50 patient-months, with a significant improvement during the last years. We conclude that OZ catheters implanted surgically through a paramedian incision have a very high survival rate and a low complication rate.

Estimating urea clearance in patients on continuous ambulatory peritoneal dialysis: a multivariate analysis.

The purpose of this study was to determine if Kt/V urea in continuous ambulatory peritoneal dialysis (CAPD) could be estimated by a multivariate model based upon simple clinical observations. The study included 439 clearance studies in 301 CAPD patients followed in 8 dialysis centers. Weekly urea clearance, 24 h urine volume and 24 h drain volume were normalized to body water by the formulae of Watson (Kt/V, UV/V and DV/V respectively). Adequate dialysis was defined as Kt/V > or = 2.0 weekly. Subjects at 2 units were used to derive the models, while others were used for model validation. Stepwise multiple linear regression was performed on the derivation set (DS) to identify the clinical variables that correlated with Kt/V. The model was then used to estimate Kt/V for the validation set (VS). In the DS, 110 clearance studies were performed in subjects with residual renal function. Multiple linear regression showed that weekly Kt/V was defined by the expression: Kt/V=1.48 + 24.1 (UV/V) + 2.92(DV/V) - 0.049 (serum creatinine) (r=0.750, p<0.001). In 204 VS studies, the correlation between estimated and measured Kt/V was 0.633. There were marked differences in the proportion of adequately dialyzed patients when Kt/V estimated from the formula shown was <2.0, between 2.0 and 2.3, and >2.3 weekly (7.9%, 54.7% and 79.7%, respectively; p2.3 weekly (8.1%, 68.8%, and 100%, respectively; p<0.001). The risk of low Kt/V can be estimated by multivariate linear models requiring only simple clinical measurements.

Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Paclitaxel has been demonstrated to have significant activity in recurrent or metastatic head and neck cancer (HNC). In addition, the combination of paclitaxel and cisplatin is active in untreated patients with inoperable HNC. Substitution of carboplatin for cisplatin allows the treatment to be delivered on an outpatient basis. PURPOSE OF THE STUDY: To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and carboplatin as first-line chemotherapy in patients with recurrent or metastatic HNC. PATIENTS AND METHODS: From March 1994 until August 1996, 49 patients with recurrent or metastatic HNC were treated with paclitaxel (200 mg/m2, by three-hour infusion) followed by carboplatin at an AUC of 7 mg.min/ml, every four weeks. G-CSF was administered prophylactically on days 2 to 12 of each cycle. There were 41 men and 8 women with a median age of 57 years (range 23-73). The majority of the patients were symptomatic and they had recurrent disease locoregionally. Fourteen patients had nasopharyngeal cancer (NPC) and 35 had squamous cell cancers of other areas of the head and neck region (non-NPC). RESULTS: At the completion of treatment, two patients with NPC demonstrated complete and six partial responses for an overall response rate of 57% (95% CI 29%-82%). Among patients with non-NPC, the response rate was 23% (95% CI 9%-37%). After a median follow up period of 15 months, the median time to progression was 4.3 months in the non-NPC group and 16.5 months in the NPC group. At the time of the analysis, median survival had not been reached in NPC while it was 7.3 months in non-NPC patients. Grade 3-4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, stomatitis, nausea/vomiting and diarrhea (4% each). CONCLUSIONS: The combination of paclitaxel and carboplatin appears to be well tolerated but only moderately active in patients with advanced non-NPC of the head and neck region. However, its activity appears promising in NPC and deserves further investigation.

Serum albumin in continuous peritoneal dialysis: absence of universal predictors.

Factors shown to affect serum albumin concentration in continuous peritoneal dialysis (CPD) were compared between two CPD populations residing in Greece (patient n = 108) and the United States (patient n = 194). Compared to the U.S. group, the Greek CPD population had higher serum albumin levels (35.1 +/- 4.6 vs 33.9 +/- 5.0 g/L, p = 0.031), was older (61.2 +/- 12.0 vs 52.7 +/- 16.5 years, p < 0.001), and had a greater number of high or high-average peritoneal solute transport types (69.4% vs 52.1%, p = 0.003). The American CPD population had a higher number of diabetics (53.1% vs 27.8%, p < 0.001), higher total Kt/Vurea (2.06 +/- 0.57 vs 1.93 +/- 0.46 weekly, p = 0.046), and higher total creatinine clearance (76.3 +/- 38.7 vs 63.4 +/- 23.5 L/1.73 m2 weekly, p < 0.001), while normalized protein nitrogen appearance values were comparable (0.95 +/- 0.21 in the Greeks vs 0.94 +/- 0.22 g/(kg x 24 hr) in the Americans, NS). A logistic regression model developed in the United States identified advanced age, diabetes, and high/high-average peritoneal solute transport as the predictors of hypoalbuminemia (serum albumin < 35 g/L). This model generated the following areas with 95% confidence intervals (CI) under the receiver operating characteristic (ROC) curve: in the Greek CPD population, ROC area 0.594 (95% CI 0.486-0.702); in the American CPD population, ROC area 0.850 (95% CI 0.810-0.890). In Greek CPD patients serum albumin appears to be affected by factors other than those identified in North America. This complicates comparisons of serum albumin, and probably morbidity and mortality, between CPD populations residing in different parts of the world.

Paclitaxel by 3-h infusion and carboplatin in anthracycline-resistant advanced breast cancer. A phase II study conducted by the Hellenic Cooperative Oncology Group.

37 patients with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 200 mg/m2 by 3-h infusion and carboplatin at an area under the curve of 7 mg.min/ml every 4 weeks with G-CSF support. There were 5 (14%, 95% CI 3-25%) complete and 11 (30%, 95% CI 15-45%) partial responders. Median duration of response was 11.5 months (range 5.2-16.8+), median time to progression 8 months (range 0.26-16.8+) and median survival 12 months (range 0.5-19.6+). Grade 3-4 leucopenia (27%), thrombocytopenia (10%) and diarrhoea (5%) were noted. In conclusion, the combination of paclitaxel and carboplatin is active and well tolerated in patients with advanced breast cancer resistant to anthracyclines.

Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution.

A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).

On the usefulness of glycylglycine in hemodialysis and peritoneal dialysis solutions.

This article reviews current knowledge on the usefulness of glycylglycine in preparing single stable hemodialysis (HD) and peritoneal dialysis (PD) solutions containing bicarbonate. The coexistence of bicarbonate and glycylglycine in a dialysis solution renders it a potent, stable buffer in which the well known reactions between bicarbonate and calcium and magnesium, and the subsequent formation of insoluble neutral calcium and magnesium carbonate salts, are avoided. Single stable bicarbonate-glycylglycine (BiGG) solutions for HD and PD have been successfully prepared and studied, both experimentally and clinically. These studies have demonstrated the advantages of BiGG solutions in terms of simplicity, stability, convenience, tolerance, biocompatibility, protection of the peritoneum, and higher ultrafiltration, compared to standard acetate or lactate solutions, and on-line prepared bicarbonate solutions. Progressive accumulation of glycylglycine or glycine, even after prolonged use, side effects, or signs of toxicity were not observed. In conclusion, BiGG solutions ensure a physiologic dialysis both from the theoretic and practical points of view.

The relationship between urine volume and drain volume as determinants of fractional urea clearance in continuous peritoneal dialysis.

A logistic regression model developed and validated in Albuquerque identified 24 hr urine volume (UV) and 24 hr drain volume/(body water) (DV/V) as predictors of fractional urea clearance (KT/V) in continuous peritoneal dialysis (CPD). Solution of this model provided DV/V values consistent with KT/V at least equal to a target KT/V for a given UV. The predictive accuracy of these unique DV/V values was tested in urea kinetic studies performed in 108 CPD patients in Thessaloniki and Athens with UV varying between 0 and 2 L/24 h. Two target weekly KT/V values, 1.70 and 1.90, were investigated. The equation DV/V = (5.2811-3.6996 UV)/ 17.554, derived by solving the logistic regression model, detected weekly KT/V > 1.70 (69/108, or 63.9% of the studies) with a sensitivity of 87.3% and a specificity of 60.4%. According to the same equation, the maximal UV consistent with weekly KT/V < or = 1.70 is 1.427 L/24 hr. The equation DV/V = (5.4994-2.6007 UV)/17.007 detected weekly KT/V > 1.90 (44/108, or 40.7% of the studies) with a sensitivity of 90.3% and a specificity of 79.2%. According to this equation, the maximal UV consistent with weekly KT/V < or = 1.90 is 2.115 L/24 hr. Determination of the lowest daily DV consistent with a target KT/V at any daily UV (within a wide range) is feasible in CPD.