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Biomedical subjects

E J Lewis

Publications and source records attributed to E J Lewis.

At least 73 records · Page 4Linked to original sources
PubMed1996

Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group.

We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.

Adolescent↗
PubMed1996

An economic analysis of captopril in the treatment of diabetic nephropathy. The Collaborative Study Group.

OBJECTIVE: The results of a recent clinical trial. The Effect of ACE inhibition on Diabetic Nephropathy, demonstrated that captopril reduced the rate of renal failure, end-stage renal disease (ESRD), and death in patients with IDDM and nephropathy. The purpose of this study was to determine the cost-benefit and cost-effectiveness of captopril as a therapy in patients with IDDM as well as the potential savings for all patients with diabetes and nephropathy. RESEARCH DESIGN AND METHODS: We used the results from a randomized, placebo-controlled trial comparing captopril (207 patients) with placebo (202 patients), whose purpose was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy to develop a model of medical treatment for patients before progression to ESRD. To model the course of illness after progression to ESRD and to extend the model to patients with NIDDM, we used data from the U.S. Renal Data System and published literature. Medical resource cost data were based predominantly upon Medicare reimbursement levels, published wholesale drug prices, and surveying health care providers. The economic model uses a payer perspective to estimate direct cost. The cost to society (indirect cost) associated with lost patient productivity due to ESRD was also estimated. Using this information, we predicted the costs incurred annually and over a lifetime if patients with IDDM and NIDDM and overt nephropathy were treated with either placebo or captopril. We also constructed a model of the overall prevalence of diabetic nephropathy to estimate the aggregate savings in total U.S. health care expenditures. RESULTS: Treatment with captopril resulted in an absolute direct cost savings or benefit of $32,550 per patient with IDDM over the course of a lifetime compared to treatment with placebo. For patients with NIDDM, the direct cost savings totaled $9,900 per patient. Absolute savings were found for indirect costs as well: $84,390 per patient with IDDM and $45,730 per patient with NIDDM. If captopril therapy were initiated in 1995 for patients with either IDDM or NIDDM and nephropathy, the aggregate health care cost savings (i.e. direct cost savings alone) would be $189 million a year for the year 1999 and $475 million a year in 2004, the present value of cumulative health care cost savings for these 10 years would be $2.4 billion. CONCLUSIONS: The use of captopril in diabetic nephropathy will provide significant savings in health care costs; in addition, it will result in savings in indirect cost, which reflects the broader societal benefit.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Drywall stilt dermatosis.

We describe a previously unreported occupational dermatosis occurring in a worker employed in drywall installation and finishing. This 50-year-old man presented with bilaterally symmetrical, parallel, linear crusted erosions on his anteromedial legs after wearing drywall stilts. The pathophysiology of this condition is considered.

Construction Materials↗
PubMed1995

The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. The Collaborative Study Group.

The purpose of this study was to determine the usefulness of a random urine specimen protein to creatinine (P/C) ratio in predicting 24-hour urine protein excretion (24 UP) in type 1 diabetic patients with overt nephropathy. Two hundred twenty-nine outpatient diabetic subjects enrolled in the Collaborative Study Group's multicenter clinical trial of "Angiotensin-Converting Enzyme Inhibition in Type 1 Diabetic Nephropathy" provided specimens for study, which encompassed a wide range of proteinuria (0.05 to 13.3 g/d). Twenty-four hour urine collections for total protein and creatinine (g/d) were obtained in the outpatient setting. This was followed shortly thereafter by an untimed single urine specimen for protein and creatinine (mg/dL). For longitudinal analysis, 33 patients provided two 24-hour urine collections with concomitant random urine specimens, separated by at least a 3-month period. Across the range of proteinuria that we studied, the log random urine P/C ratio correlated to log 24 UP (r = 0.90). The regression line was almost identical to the line of unity, which indicates that a patient's 24 U/P (in g/d) can be predicted directly from the random urine specimen P/C ratio (P/C = 24 UP in g/d). However, the standard deviations associated with these predictions were large, especially at the higher 24 UP values. Of the 33 patients who provided two time-separated specimens, the direction of change in P/C ratio was discordant with the direction of change in 24 UP in 14 of the 33 repeat specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relationship between appearance of urinary red blood cell/white blood cell casts and the onset of renal relapse in systemic lupus erythematosus.

The purpose of the study was to determine the extent to which urinary sediment findings (changes in red blood cells [RBCs], white blood cells [WBCs], and the appearance of RBC and WBC casts) predict the onset of renal relapse (defined as a specific increase in proteinuria and/or serum creatinine level) in patients with systemic lupus erythematosus (SLE). Seventeen SLE patients with biopsy-proven diffuse proliferative glomerulonephritis at initial presentation were followed prospectively for 1,129 patient-months under a study protocol. Semiquantitative urinalyses were performed at 2-month intervals during periods with little or no SLE activity and, more frequently, during periods with increased SLE activity. Each urinalysis was accompanied by a clinical evaluation and a panel of screening tests relevant to the evaluation of SLE activity. During this study, 877 semiquantitative urinalyses were performed and 43 renal relapses were observed in 14 patients. No relapse occurred in three patients. Of the renal relapses, 30 were defined as proteinuria relapses (mean baseline proteinuria increased from 0.8 +/- 0.1 g/24 hr to 2.7 +/- 0.3 g/24 hr; P < 0.001) and 13 were defined as serum creatinine relapses (mean baseline serum creatinine increased from 2.7 +/- 0.4 mg/dL to 3.8 +/- 0.5 mg/dL; P < 0.001). Red blood cell and/or WBC casts (cellular casts) were observed before or at the onset of 35 of the 43 renal relapses (sensitivity, 81%). The mean and median intervals between the appearance of cellular casts and the onset of renal relapse was 10 +/- 2 weeks and 8 weeks, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗
PubMed1995

A negative regulatory element in the rat dopamine beta-hydroxylase gene contributes to the cell type specificity of expression.

Dopamine beta-hydroxylase (DBH) catalyzes the synthesis of the neurohormone norepinephrine and is expressed only in noradrenergic and adrenergic cells of the nervous and endocrine systems. We have previously described a positive-acting genetic regulatory element of the DBH that contributes to the restricted expression of this gene. In the study described here, we identify and characterize a negative-acting regulatory element within the 5'-flanking region of the rat DBH gene. This negative regulatory element, which is located between -282 and -232, represses transcription from the DBH promoter in cell lines of noncatecholaminergic origin and binds to nuclear factors found in extracts from both the catecholaminergic cell line SHSY-5Y and the noncatecholaminergic cell lines JEG-3 and C6. The negative regulatory region will reduce transcription from a heterologous promoter in two noncatecholaminergic cell lines. These experiments demonstrate that the selective expression of the DBH gene is controlled by both positive- and negative-acting genetic regulatory elements.

Animals↗
PubMed1995

The study of the effect of intensity of blood pressure management on the progression of type 1 diabetic nephropathy: study design and baseline patient characteristics. Collaborative Study Group.

A randomized, prospective, clinical trial has been initiated to continue follow-up in a subset of the patients previously enrolled in the recently completed Study of Angiotensin-Converting Enzyme Inhibition (ACEi) in Type 1 Diabetic Nephropathy. In that study, the use of captopril was associated with a 48% reduction in the risk of doubling the serum creatinine and a 50% reduction in the risk of experiencing dialysis, transplantation, or death, compared with the use of placebo. These effects were independent of captopril's effect on the blood pressure. This study is designed to determine whether the level of mean arterial blood pressure (MAP), using the ACE inhibitor ramipril as the primary therapy, is associated with an improved prognosis of diabetic nephropathy with respect to (1) the rate of decline in renal function; (2) the rate of progression to end-stage renal failure; (3) the clinical course of proteinuria; (4) morbidity; and (5) mortality. Patients are randomized into one of two distinct blood pressure control groups, an Intensive Group #1, MAP < or = 92 mm Hg; and a Moderate Group #2, MAP 100 to 107 mm Hg. Patients previously enrolled in the "Study of ACEi in Type 1 Diabetic Nephropathy" whose serum creatinine was less than 4.0 mg/dL (354 mumol/L) were eligible for randomization into this study. All patients will receive ramipril (2.5 to 10.0 mg/day) as the primary therapy, with the addition or removal of other antihypertensive agents as needed to achieve the assigned blood pressure goal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A homeodomain protein selectively expressed in noradrenergic tissue regulates transcription of neurotransmitter biosynthetic genes.

In order to characterize the specificity of expression of the neurotransmitter biosynthetic gene dopamine beta-hydroxylase (DBH), the identification of proteins that interact with the DB1 enhancer was initiated. A homeobox-containing cDNA was isolated from a PC12 expression cDNA library screened with the DB1 enhancer. The homeodomain is a member of the paired-like class, and is encoded by several nonidentical cDNAs. The cDNAs contain the same sequence in the homeodomain and 3' coding and noncoding sequences, but diverge in sequence 5' to the homeodomain. This family of homeobox-containing cDNAs is named Arix. Arix mRNA transcripts are found only in noradrenergic, DBH-positive tissues, and in cell lines derived from those tissue. The DB1 enhancer contains two binding sites for the Arix homeodomain, and both sites contribute to basal activity of the DBH promoter. When introduced into tissue culture, Arix regulates the transcriptional activity from the DBH promoter, and also from the promoter of the tyrosine hydroxylase gene, encoding the initial enzyme of the catecholamine biosynthetic pathway. The pattern of expression of the Arix transcripts, the presence of the homeodomain, and the transcriptional regulatory properties suggest that this family of proteins may be involved in the specificity of expression of the catecholamine biosynthetic genes.

Amino Acid Sequence↗
PubMed1994

The fibrillary glomerulopathies.

Fibrillary glomerulopathy is a category of glomerular disease that is defined by the ultrastructural feature of organized deposits of extracellular, nonbranching, microfibrils. The best-known disease in this category is amyloidosis, but cryoglobulinemia, light chain deposition disease, systemic lupus erythematosus, immunotactoid glomerulopathy, and diabetic fibrillosis may have similar ultrastructural findings and comprise the differential diagnosis of the fibrillary glomerulopathies. Because they have disease-specific therapeutic and prognostic implications, differentiating among these entities is important for nephrologists and nephropathologists. To aid the physician, we will review the fibrillary glomerulopathies using an algorithm based on morphology, clinical features, and serologic assessment. We believe this approach will prove to be practical and useful to the practicing nephrologist.

Actin Cytoskeleton↗
PubMed1994

Primary focal segmental glomerulosclerosis: clinical course and response to therapy.

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.

Glomerulosclerosis, Focal Segmental↗
PubMed1994

Remission of nephrotic range proteinuria in type I diabetes. Collaborative Study Group.

The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (> 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be < or = 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 +/- 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗