A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group

BACKGROUND: The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation. The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy. METHODS: In a multicenter, placebo-controlled, randomized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 g; the placebo was a similar dose of olive oil. Serum creatinine concentrations, elevated in 68 percent of the patients at base line, and creatinine clearance were measured for two years. The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study. RESULTS: Fifty-five patients were assigned to receive fish oil, and 51 to receive placebo. According to Kaplan-Meier estimation, 3 patients (6 percent) in the fish-oil group and 14 (33 percent) in the placebo group had increases of 50 percent or more in their serum creatinine concentrations during treatment (P = 0.002). The annual median changes in the serum creatinine concentrations were 0.03 mg per deciliter (2.7 mumol per liter) in the fish-oil group and 0.14 mg per deciliter (12.4 mumol per liter) in the placebo group. Proteinuria was slightly reduced and hypertension was controlled to a comparable degree in both groups. The cumulative percentage of patients who died or had end-stage renal disease was 40 percent in the placebo group after four years and 10 percent in the fish-oil group (P = 0.006). No patient discontinued fish-oil treatment because of adverse effects. CONCLUSIONS: In patients with IgA nephropathy, treatment with fish oil for two years retards the rate at which renal function is lost.     

Characteristics of children with acute nonlymphocytic leukemia in long-term continuous remission: a report for Childrens Cancer Study Group

Children and young adults less than 18 years of age with acute nonlymphocytic leukemia who remained in long term bone marrow and extramedullary remission for two years or longer since starting maintenance were compared to the remaining responders for the following characteristics: cell type, sex, age at diagnosis, race, pretreatment, white blood count, length of time from start to induction therapy to achievement of an M1 marrow, marrow rating at day 56 of therapy, marrow rating at the start of maintenance therapy, and specific study. Forty-eight patients of a group of 333 qualified as having long term remission (14.4%). Multivariant analysis indicated that patients between the ages of 3 and 10 years (p = 0.003) as well as the length of time to achieve an M1 marrow from the start of treatment (p = 0.03) were the only characteristics associated with achievement of a long term remission. Maintenance therapy was discontinued in 15 patients from 2.5 to 4.8 years after start of maintenance and all patients remained in bone marrow remission of periods from 0+ to 3.0+ years after stopping treatment. Of the 33 who have remained on a continuous maintenance therapy 12 have had bone marrow relapses. These data confirm the prognostic value of age and length of time to achieve remission during induction in acute nonlymphocytic leukemia and suggest that there may be no significant benefit from maintenance therapy continued beyond 2 years for patients in their initial remission.     

Long-term prognosis for tonsillectomy patients with IgA nephropathy

A retrospective study of 85 patients with IgA nephropathy was undertaken to determine the long-term effect of tonsillectomy. Forty-three patients (24 males and 19 females) had received tonsillectomies (Group A) and 42 patients (17 males and 25 females) had not (Group B). These patients had been followed up for more than 5 years after renal biopsy. The average age at the initial renal biopsy was 25.72 years in Group A, and 33.16 years old in Group B. The average period of renal biopsy to tonsillectomy in Group A was 10.47 months. The average follow-up period was 8 years and 9 months in both groups. At the beginning of treatment, the two groups were well matched in terms of creatinine clearance, urinalysis, and blood pressure. Six patients in Group A and eight patients in Group B were treated with steroids. The glomerular injury detected at the renal biopsy was more extensive in Group A than in Group B. Renal function in the two groups was compared. The clinical remission rate in Group A was significantly higher than in group B (P<0.05). The stable renal function rate in Group A was significantly higher than in Group B (P<0.05). The renal survival rate was 97.7% in Group A and 83.3% in Group B, but there was no significant difference between the two groups. Histologically, the rate of remission of the minor lesion in Group A was significantly higher than in Group B (P < 0.05). Our results showed that tonsillectomy for IgA nephropathy was clinically of great value.     

Functional recognition of in vivo processed self antigen

Of 531 cases of immunoglobulin A nephropathy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective analysis to have proteinuria > or = 1 g/d. These patients have been followed a minimum of 3 months (range, 3 to 121 months). Monitoring in the registry included routine blood pressure estimates and renal function status by serum creatinine, creatinine clearance, and proteinuria. These patients were grouped and examined retrospectively into three categories (1) hypertensive on angiotensin-converting enzyme (ACE) inhibitor therapy (ACEi), (2) hypertensive on other medication, and (3) no hypertension (NT). Despite comparable renal function abnormalities, the 27 ACEi patients, when compared with the 55 patients receiving other medication, experienced a significantly slower rate of decline in renal function as measured by slope of creatinine clearance (-0.4 mL/min/mo v-1.0 mL/min/mo; P = 0.007), longer time to a loss of one third of baseline creatinine clearance (P = 0.004), and a higher percentage of remission in proteinuria (18.5% v 1.8%; P = 0.003). A subsequent comparison was made between the NT and ACEi groups and, despite a much lower initial serum creatinine, less severe pathology, and a longer observation period in the NT group, both the rate of decline of creatinine clearance (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) and the percentage of patients progressing to renal failure (21.2% v 18.5; P = 0.8) were not different. The remission rate of proteinuria was superior in the ACEi-treated group compared with the NT group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus

BACKGROUND: Several studies had suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. METHODS: We prospectively studied the prevalence of NDRD among a Chinese NIDDM population. Renal biopsy specimens were evaluated with light-, immunohistological and electron-microscopy. The cohort consisted of 51 patients who had NIDDM and proteinuria > 1 g/24 h. RESULTS: Patients with both isolated diabetic nephropathy (DN, n = 34) and NDRD (n = 17) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and glycosylated haemoglobin levels, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had microscopic haematuria (P = 0.043) or non-nephrotic proteinuria (P = 0.004). IgA nephropathy accounted for 59% of the NDRD identified. CONCLUSIONS: In this study, microscopic haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients presenting with renal disease.     

Renogram deconvolution in the management of diabetic nephropathy: utility of the measurement of initial tracer uptake

Our objective was to assess mean transit time (MTT) and initial uptake, both parameters derived from the renal retention function (RRF), in the study of renal function in patients with diabetic nephropathy. We studied 25 patients, 7 with type I diabetes mellitus and 18 with type II diabetes mellitus, all of whom fulfilled the criteria for diabetic nephropathy with proteinuria and/or retinopathy. We found a statistically significant correlation between initial uptake and the other biochemical and renographic parameters studied except proteinuria: serum creatinine (r = 0.66, P < 0.002), creatinine clearance (r = 0.61, P < 0.003), glomerular filtration rate (r = 0.74, P < 0.003) and effective renal plasma flow (r = 0.66, P < 0.003). The other renographic parameters studied (maximal activity of the conventional renogram and MTT of the deconvoluted renogram) did not show any correlation. Initial uptake is a semi-quantitative renographic parameter that can provide complementary information to biochemical data and it may be useful in the management of diabetic nephropathy, especially in patients with high serum creatinine or creatinine clearance.     

Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes

OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.     

Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.     

The treatment with levamisole of frequently recurring steroid-sensitive idiopathic nephrotic syndrome in children

BACKGROUND AND OBJECTIVE: The treatment of frequently relapsing steroid-sensitive nephrotic syndrome in children with established immunosuppressive drugs (steroids, cyclophosphamide, cyclosporin A) sometimes presents problems because of the expected incidence of side effects. Stimulation of the immune system with the anthelminthic drug levamisole in this disease has been documented. Aim of this study was to assess in a prospective but uncontrolled series of observations its value and side effects. PATIENTS AND METHODS: 25 patients (15 boys, ten girls; median age 10 [3.5-22] years) were given levamisole, 2 mg/kg/48 h. Before this treatment was started eight of the children/adolescents (32%) had frequent relapses and 17 (68%) had become steroid-dependent. Treatment was started during steroid-induced remission and continued for 3-24 (median 6) month, while steroids were discontinued after four weeks. RESULTS: Relapse frequency per patient month was reduced from a mean of 0.5 (0.33-0.83) before to 0.31 (0-0.67) during levamisole administration (P < 0.001). In 12 patients (48%) no or considerably fewer relapses were observed. Patients with exclusively frequent relapses responded to levamisole better than those with steroid dependence (7/8 [87.5%] vs. 5/18 [27.7%], P = 0.01). Side effects were reversible leukopenia in two patients and nonspecific skin rash as well as epigastric pain in one patient. CONCLUSION: Levamisole is an efficacious addition or alternative, with a low incidence of side effects, in the treatment of frequently relapsing nephrotic syndrome, particularly so in yet steroid-dependent patients.     

Local recurrence versus new primary: clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting

PURPOSE: The purpose of this study was to perform a detailed clinical pathological analysis of breast relapses in patients treated with conservative surgery and radiation therapy in an effort to classify those relapses as true local recurrences or second primary tumors, and to assess the prognostic and therapeutic implications of such a classification system. METHODS AND MATERIALS: Of 990 patients treated with conservative surgery and radiation therapy at our facilities prior to December 1987, 82 patients have experienced a relapse in the conservatively treated breast as the primary site of failure. Patients were classified as having new primary tumors if they fulfilled any one of the following criteria: a) breast relapse occurring at a site distinctly removed from the original tumor; b) histology of the breast relapse compared with the original tumor consistent with a new primary; or c) DNA flow cytometry converting from an aneuploid primary to a diploid relapse. RESULTS: As of 2/92, with a median follow-up of 5.4 years from the time of breast relapse, the overall 5-year survival rate following breast relapse was 55%. Forty-seven patients were classified as true recurrences and 33 patients were classified as new primaries. Patients classified as true recurrences had a shorter median time to breast relapse than patients classified as new primaries (3.16 years vs. 5.42 years, p < .05) and an inferior post breast recurrence survival rate compared to patients classified as new primaries (36% vs. 89%, p < .05). Residual disease outside of the recurrent tumor bed was also noted to be more frequent in patients classified as true recurrences compared to patients classified as new primaries (48% vs. 16%, p < .05). CONCLUSION: Based on the clinical and pathological criteria outlined, it appears that a significant portion of patients experiencing a relapse in the conservatively treated breast may have new primary tumors as opposed to true local relapses. Distinction between a true recurrence and a new primary tumor may have significant prognostic implications. Uncertainties associated with the clinical and pathological criteria are presented and further investigations with genetic fingerprinting techniques to establish the clonality of breast relapses are presented and discussed.     

The prognostic significance of chromosomal analysis and immunophenotyping in 117 patients with de novo acute myeloid leukemia

Chromosomal abnormalities is one of the most important prognostic factors in acute myeloid leukemia (AML). Other parameters which may influence the prognosis include age, French-American-British-type, clinical variables and possibly the expression of certain immunophenotypic surface makers. However, only rarely has the expression of these markers been analyzed in multivariate models including the information from cytogenetics and clinical variables. We conducted a retrospective study of 117 consecutive adult patients with de novo AML diagnosed and treated in our institution during a 6-year period. Following standard induction chemotherapy with daunomycin and cytosine arabinoside 75 patients (64%) achieved complete remission (CR). The overall 5 year survival rate was 23% and, for patients achieving CR, 30%. When all patients were analyzed age, chromosomal aberration and lack of CD33 expression were of independent prognostic value. The overall 5 year survival rate was 28% for patients aged 55 years or younger, 25% for patients aged 56-65 years and 4% for those > 65 years, P = 0.041. Patients with good-risk chromosomal abnormalities presented an overall 5 year survival of 36%, compared to 25% in patients with normal karyotype, 22% in patients with intermediate risk abnormalities and 5% in patients with poor-risk abnormalities, P = 0.004. Patients with CD33+ myeloblasts had an overall survival of 25% at 5 years compared to 0% in the CD33- patients, P = 0.021. Analysis of the expression of CD7, CD34 and terminal deoxynucleotidyl transferase on myeloblasts had no impact on overall survival in a multivariate analysis. Thus, this study confirmed the prognostic value of age and cytogenetic risk group and defined CD33 as a novel factor of independent prognostic importance in adult de novo AML.     

Histopathologic findings from 2-year protocol biopsies from a U.S. multicenter kidney transplant trial comparing tarolimus versus cyclosporine: a report of the FK506 Kidney Transplant Study Group

BACKGROUND: This paper reports the histopathologic results of 2-year protocol biopsies from patients who were enrolled in the U.S. FK506 kidney transplant study . METHODS: Recipients of cadaveric kidney transplants were randomized to tacrolimus or cyclosporine therapy. Patients active in the trial at 2 years after transplantation were approached for a protocol biopsy. Biopsies were scored by the Banff classification in a blinded fashion by one pathologist. RESULTS: A total of 144 patients (41.3% of those active at 2 years) had a 2-year protocol biopsy performed; 79 patients were treated with tacrolimus and 65 patients were treated with cyclosporine. Evidence of acute rejection was found in seven (8.9%) of the 2-year biopsies in tacrolimus-treated patients and six (9.2%) cyclosporine-treated patients. Chronic allograft nephropathy was found in 49 (62.0%) tacrolimus biopsies and 47 (72.3%) cyclosporine biopsies (P=0.155). There were no apparent histopathologic differences between the tacrolimus and cyclosporine biopsies. The occurrence of chronic allograft nephropathy was significantly higher in patients who received a graft from an older donor (P<0.01), who experienced presumed cyclosporine or tacrolimus nephrotoxicity (P<0.001), who developed a cytomegalovirus infection (P=0.038), or who experienced acute rejection in the first year after transplantation (P=0.045). A multivariate analysis showed that nephrotoxicity and acute rejection were the most significant predictors for chronic allograft nephropathy. CONCLUSIONS: The occurrence of histologic acute rejection was rare at 2 years, confirming the absence of subclinical acute rejection in these late biopsies. A majority of the biopsies showed features consistent with chronic allograft nephropathy that was associated with acute rejection (particularly in cyclosporine-treated patients), nephrotoxicity, and cytomegalovirus infection in the first year. This suggests that nonimmunologic factors, such as drug-induced toxicity, may play an important role in chronic allograft nephropathy.     

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.     

Hearing loss from combined exposures among petroleum refinery workers

Seventy-three consecutive cases of childhood acute lymphoblastic leukemia (ALL) diagnosed and managed in Queen Mary Hospital over a 10-year period from 1985 to 1994 were retrospectively analysed for their presenting features and treatment outcome. The 48 boys and 25 girls ranged in age from 0.4 to 14.2 years (median: 4.3 years). Bone and joint pain was a relatively common presenting feature besides fever, hepatosplenomegaly and lymphadenopathy. Immunophenotyping of blast cells showed: 51 B-cell precursor ALL, one B-ALL, 10 T-ALL and three myeloid-antigen positive ALL. Eight cases were unclassified since immunophenotyping had not been performed. Out of the 73 patients, treatment outcome was analysed in 20 cases treated with UKALL-VIII regimen and 28 cases treated with either the UKALL-XI regimen or the Hong Kong Children Cancer Study Group (HKCCSG) protocol which was modelled upon UKALL-XI. Although complete remission rates were similar between the two groups, patients treated with the former regimen that was less intensified suffered more relapses than the latter (56 per cent versus 21 per cent, P = 0.04). There were, however, no significant differences both in event-free survival (38.2 +/- 11.2 per cent versus 71.3 +/- 9.3 per cent, P = 0.12) and overall survival (70.0 +/- 10.2 per cent versus 79.6 +/- 8.3 per cent, P = 0.41) between the two groups at 3 years by long-rank test. With the use of risk-directed therapy and improved supportive care, two-thirds of our patients are able to enjoy long-term event-free survival.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.     

Autonomous proliferation of leukemic cells in vitro as a determinant of prognosis in adult acute myeloid leukemia

BACKGROUND AND METHODS: A characteristic of acute myeloid leukemia is the frequent ability of the leukemic cells to sustain their own proliferation in vitro. To determine the clinical importance of this property, we measured the uptake of tritiated thymidine by leukemic cells in serum-free and cytokine-free cultures as a means of determining the rate of spontaneous proliferation in 114 patients with newly diagnosed acute myeloid leukemia. Proliferation was then classified according to three quantitative levels of activity and related to overall survival and to treatment outcome (the response to treatment, the actuarial probability of relapse, and disease-free survival) in 91 patients who were treated with chemotherapy to induce remission. RESULTS: Of the 114 patients, 37 had low, 39 had intermediate, and 38 had high levels of proliferation. The probability of survival at three years was 36 percent among patients with low levels of proliferative activity and 3 percent among those with high levels (P < 0.001). Among the patients treated with chemotherapy, those with low rates of proliferative activity had a 68 percent rate of complete remission and a 49 percent probability of remaining free of relapse, whereas those with high rates of proliferative activity had only a 39 percent rate of complete remission (P = 0.04) and an 11 percent probability of remaining in complete remission (P = 0.009). The probability of disease-free survival at three years among the patients in complete remission after chemotherapy was 49 percent among those with low rates of proliferative activity and 9 percent among those with high rates (P = 0.004). Accordingly, patients with low rates of proliferative activity also had a significantly higher rate of overall survival (44 percent vs. 4 percent; P = 0.002). Patients whose cells had intermediate levels of proliferation in vitro had intermediate rates of survival, relapse, and disease-free survival. CONCLUSIONS: The capacity of leukemic blasts for autonomous proliferation is associated with highly aggressive acute myeloid leukemia.     

A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome

To compare the efficacy (induction of remission) and safety of cyclosporine (CsA) with those of supportive therapy in patients with steroid-resistant idiopathic nephrotic syndrome (INS), we organized an open, prospective, randomized, multicentric, controlled study for parallel groups, stratified for adults and children. Forty-five patients with steroid-resistant INS were randomly assigned to supportive therapy or CsA (5 mg/kg/day for adults, 6 mg/kg/day for children) for six months, then tapered off by 25% every two months until complete discontinuation. Four patients were lost to follow-up. During the first year 13/22 CsA-treated patients versus three of 19 controls attained remission of the nephrotic syndrome (P < 0.001). A symptom score was assessed at time 0 and at six months. The mean score significantly decreased in the CsA group (P < 0.001), but remained unchanged in the controls. At month 6 the mean urinary protein excretion, the mean serum proteins and plasma cholesterol had significantly improved in the CsA group but were not changed in the controls. There were no significant differences in serum creatinine and creatinine clearance between treatments (interaction time* treatments, P = 0.089 and P = 0.935, respectively) at month 6 versus basal. The CsA-related side-effects were mild; no significant difference in blood pressure between the two groups was seen at any time. This study shows that CsA can bring about remission in some 60% of patients with steroid-resistant INS. In patients with normal renal function and without severe hypertension, CsA at the therapeutic scheme adopted did not produce severe renal or extrarenal toxicity.     

Renal sonography: can it be used more selectively in the setting of an elevated serum creatinine level?

The objectives of our study were to (1) assess the outcomes resulting from the use of sonography in patients referred to our institution's ultrasound laboratory for an elevated serum creatinine level and (2) determine relevant clinical parameters in these patients to better triage them for sonography. We retrospectively identified and determined outcomes of 60 patients (20 women, 40 men; mean age, 61 years; range, 33 to 100 years) referred for sonographic evaluation because of an increased serum creatinine level (> or = 1.3 mg/dL). Ultrasound findings (hydronephrosis, renal size, and echogenicity) were correlated with clinical outcomes. Twenty-one patients (35%) had hydronephrosis, with 14 of these patients confirmed to be obstructed and five not obstructed. Two were indeterminate for obstruction. Eight of 14 obstructed patients were successfully treated. All obstructed patients had a suggestive history for obstruction with at least one of the following: pelvic mass (n = 9), stone disease (n = 4), or flank pain (n = 1). Only 2 of 44 patients, who were not obstructed, had any of these parameters (statistically significant difference, P < 0.0001). Thirty of the patients, who were not obstructed, had more likely alternative causes for renal failure, with sonography having no effect on patient management. Renal size and echogenicity had little effect on patient management. Sonography was efficacious in guiding management in patients with a suggestive history for obstruction (eg, pelvic mass, stone disease, or flank pain) but not in most patients who had no suggestive history and other more likely causes for renal failure.     

Non-Hodgkin's lymphomas of stage III extent. Is total lymphoid irradiation appropriate treatment?

Many investigators have regarded Stage III lymphomas as a generalized form of disease and have accordingly recommended systemic treatment programs. Between 1961 and 1973, 68 patients with clinical or pathologic Stage III non-Hodgkin's lymphomas were seen in the Division of Radiation Therapy at Stanford University Medical Center and were treated by high dose (3500 rads or more) total lymphoid radiation therapy only. Of the 17 patients who had a diffuse histologic pattern, the actuarial survival at 5 years was 39%, but only three patients have remained free of disease. In contrast, for the 51 patients who had a nodular histologic pattern, the actuarial survivals at 5 and 10 years were 75% and 65%, respectively. Corresponding relapse-free survivals for patients with nodular lymphomas were 43% and 33%, respectively. Of 28 patients who relapsed with nodular lymphomas, 18 (64%) had relapses confined to lymph nodes; six of these were extensions to previously unirradiated epitrochlear-brachial nodes. Seven of the 18 patients were treated only with further conventional external radiation therapy at the time of their relapses and remain free of disease for additional periods of 2 to 5 years. Hence, 30 of 51 (59%) patients with nodular lymphomas have thus far been controlled by high dose total lymphoid irradiation only. Over 90% of relapses among patients with nodular lymphomas were seen within the first 5 years. The data suggest that high dose conventional radiation therapy to incorporate not only the routine total lymphoid fields but also the epitrochlear, mesenteric, and Waldeyer's ring region has curative potential even in Stage III non-Hodgkin's lymphomas, especially in the nodular group.     

Renal artery stenosis and chronic renal failure in NIDDM

The NIDDM patient, willingly with high blood pressure and atheroma, has frequently an abnormal renal function. Must a renal artery stenosis (RAS) be searched as a determining or favorising cause? We have searched RAS by color duplex scan, in 60 consecutive NIDDM patients with altered renal function (creatinine clearance < or = 60 mL/min). Metabolic blood pressure (ABPM), cardiovascular and renal investigations have been realised. The population was composed of 22F/38M with middle age: 70.7 +/- 6.2 yrs, diabetic duration: 11.6 +/- 8 yrs, the plasma creatinine was: 161 +/- 78 mumol/L and clearance: 40 +/- 13 mL/min. Thirty eight had albuminuria, 28 had plasma creatinine > or = 150 mumol/L. All patients had high blood pressure. Significative RAS (> or = 70%) was detected in 15 patients (25%) by color duplex scan and proved with arteriography (n = 10) or angio NMR (n = 5). Twelve (80%) had unilateral stenosis (4 thrombosis), 3 (20%) bilateral stenosis. Renal US lead the diagnosis in 10 patients (66%): unilateral or bilateral hypotrophy. Those 15 patients had these following characteristics: 4F/11M (sex R : 0.36), middle age: 70.8 +/- 7.2 yrs, diabetic duration: 14.3 +/- 7.5 yrs, HbA1c was at 8.4 +/- 2%, 8 (53%) patients require insuline and 5 have retinopathy, plasma creatinine was at 169 +/- 6 mumol/L; 32% of patients with plasma creatinine > or = 150 mumol/L had RAS (n = 9/60%), creatinine clearance was at 38 +/- 12 mL/min (7/47% < or = 30 mL/min), 9 (60%) had macroalbuminuria and 5 (33%) microalbuminuria. All hypertensive patients were treated (mean SBP: 148 +/- 16, mean DBP: 82 +/- 7 mmHg) and had 62 +/- 28% SBP escape and 33 +/- 19% DBP escape. Ten had severe hypertension (at least 3 hypotensive drugs), 12 received CEI; 8 (53%) were smokers; 14 (93%) had one or more macroangiopathies (10/66% coronary heart diseases, 7/46% lower limbs arteritis, 6/40% carotid atheroma); 13 of these macroangiopathies are severe. In conclusion, renal failure (especially evolutive and/or treated with CEI) in NIDDM must call up a RAS (25%) specially in elderly males with a long diabetes duration, severe hypertension and macroangiopathies. This patient profile must lead to a color duplex scan to confirm the diagnosis already suspected by the renal echography.