Multisite evaluation of a new dipstick for albumin, protein, and creatinine.

The goal of our study was to perform a multisite evaluation of a new urine dipstick called Multistix PROtrade mark (Bayer, Elkhart, IN), which has reagent pads for the simultaneous assay of urinary albumin, protein, and creatinine. Patients' urine specimens were assayed at four sites with these dipsticks and with the familiar Bayer Multistix 10SG dipsticks for protein. The new dipstick pads for albumin are impregnated with bis (3',3"-diiodo-4',4"-dihydroxy-5',5"-dinitrophenyl)-3,4,5,6-tetrabromo-sulfonephthalein (DIDNTB) dye. These dipsticks also have a novel pad that estimates urinary creatinine using the peroxidase activity of the copper-creatinine complex. We determined the interlaboratory agreement of these dipsticks by comparing dipstick results to values obtained by quantitative analytical methods. We found that dividing the dipsticks' albumin or protein results by the creatinine concentration reduced the number of false-positive albumin or protein values observed in concentrated urines, and reduced the number of false negatives in dilute urines. The ratio of albumin to creatinine, or protein to creatinine gives a better measure of albumin or protein excretion. Compared to reading by eye, the dipstick results agreed better with the quantitative assays when they were read by a reflectometer (Bayer Clinitek).

Albuminuria and proteinuria in hospitalized patients as measured by quantitative and dipstick methods.

We tested patients' urines for albumin, protein, and creatinine by quantitative and dipstick methods. The concentrations of these analytes were established by quantitative, cuvet-based chemistry methods that we assumed gave the "correct" values. There was good to excellent agreement of the dipstick results with the quantitative methods for the above three analytes. We found many patients who excreted pathological amounts of albumin and/or protein who did not have a diagnosis of kidney disease or other likely causes of proteinuria, suggesting that albuminuria and/or proteinuria were underdiagnosed in our group of patients. Those with cardiovascular disease, kidney disease, or diabetes showed the greatest predictive value of a positive test for albumin or protein by dipstick. Dipstick testing for albumin, protein, and creatinine had good or excellent agreement with quantitative methods. The dipstick tests were easy to use, simple, and low in cost, and can serve well for point-of-care testing.

Cost-effectiveness of sevelamer versus calcium carbonate plus atorvastatin to reduce LDL in patients with chronic renal insufficiency with dyslipidemia and hyperphosphatemia.

We conducted a cost-effectiveness analysis to compare costs and clinical outcomes of sevelamer versus calcium carbonate plus atorvastatin for treatment of dyslipidemia in patients with chronic renal insufficiency. The model was from the third-party payer perspective. Efficacy and adverse event rates for each regimen were obtained from published clinical trials. Drug costs were based on average wholesale prices; monitoring costs were based on Medicare reimbursement rates. Our model suggests that the combination of calcium carbonate plus atorvastatin is substantially more cost-effective than sevelamer in reducing low-density lipoprotein (LDL) in these patients. One-way sensitivity analyses were performed to assess if 25% and 50% price reductions in sevelamer affected overall cost-effectiveness results. A 50% sevelamer price reduction was less expensive than combination therapy but remained less cost-effective. A two-way sensitivity analysis on the probability that a patient achieves the goal of a 35% LDL reduction resulted in calcium carbonate plus atorvastatin remaining more cost-effective. Further cost-effectiveness studies are necessary to corroborate our data.

Urinary protein and albumin excretion corrected by creatinine and specific gravity.

Timed urine collections are difficult to use in clinical practice owing to inaccurate collections making calculations of the 24-h albumin or protein excretion questionable. One of our goals was to assess the 'correction' of urinary albumin and (or) protein excretion by dividing these by either the creatinine concentration or the term, (specific gravity-1)x100(1). The 24-h creatinine excretion can be estimated based on the patients' gender, age and weight. We studied the influence of physiological extremes of hydration and exercise, and protein and creatinine excretion in patients with or suspected kidney disorders. Specimens were collected from healthy volunteers every 4 h during one 24-h period. We assayed the collections individually to give us an assessment of the variability of the analytes with time, and then reassayed them after combining them to give a 24-h urine. For all volunteers, the mean intra-individual CVs based on the 4-h collections expressed in mg/24 h were 80.0% for albumin and 96.5% for total protein (P0.2). The CVs were reduced by dividing the albumin or protein concentration by the creatinine concentration or by the term, (SG-1)x100. This gave a CV for mg albumin/g creatinine of 52% (P<0.1 vs. albumin mg/g creatinine); mg protein/g creatinine of 39% (P<0.05 vs. mg protein/g creatinine); mg albumin/[(SG-1)x100] of 49% (P<0.1 vs. albumin)/[(SG-1)x100]; and mg protein/[(SG-1)x100] of 37% (P<0. 05 vs. mg protein)/[(SG-1)x100]. For the 68 subjects in the study, the strongest correlation was between the creatinine concentrations and the 24-h urine volume: r=0.786, P<0.001. The correlation of (SG-1)x100 vs. the 24-h urine volume was: r=0.606, P<0.001; for (SG-1)x100 and the creatinine concentration, the correlation was: r=0.666, P<0.001. Compared to the volunteers, the albumin and protein excretion in mg/24 h were more variable in the patients. The same was true if the albumin or protein concentrations were divided by the creatinine concentration or by (SG-1)x100. Protein and albumin concentrations were lower in dilute urines. Dividing the albumin or protein concentrations by the creatinine concentration reduced the number of false negative protein and albumin results. Dividing the albumin or protein values in mg/24 h by (SG-1)x100 eliminated fewer false negatives. Albumin concentrations increased significantly after vigorous exercise. The increase was almost eliminated when the albumin result was divided by the creatinine concentration suggesting that a decreased urine flow and not increased glomerular permeability causes an increase of post-exercise albuminuria. The same was true for proteinuria. A dipstick test plus an optical strip reader that can measure urine protein, albumin, and creatinine and calculate the appropriate ratios provides a better screening test for albuminuria or proteinuria than one measuring only albumin or protein.

Assay of creatinine using the peroxidase activity of copper-creatinine complexes.

OBJECTIVES: It was our goal to develop a urine dipstick that could measure creatinine with a peroxidase reaction. The simultaneous measurement of albumin and creatinine permits the estimation of the 24-h albumin excretion, an important value in judging existing or likely development of renal failure. A highly sensitive dye-binding dipstick method for albumin exists, and a suitable dipstick for the assay for urine creatinine is described here. METHODS: Copper-creatinine and iron-creatinine complexes have peroxidase activity. With 3,3',5,5'-tetramethylbenzidine (TMB), and diisopropyl benzene dihydroperoxide (DBDH); the peroxidase activity of copper-creatinine and iron-creatinine complexes can be demonstrated. This reaction was used in the assay of urine creatinine either in solution or by a suitably impregnated urine dipstick. RESULTS: Our method based on the peroxidase activity of the copper-creatinine complex has an analytical range for creatinine of 100 mg/L (0.884 mmol/L) to 3000 mg/L (26.52 mmol/L). The creatinine assay is free from most interfering compounds that may be present in urine. Hemoglobin is an interferent, and its effects can be reduced but not eliminated by the addition of 4-hydroxy-2-methyl quinoline. We do not recommend using the dipsticks when visible blood is present or if the dipstick blood test is positive. The copper-creatinine complex oxidizes ascorbic acid; however, we were able to modify the reaction conditions so that ascorbic acid at < 4.4 g/L does not interfere. We found good agreement on fresh urines between the creatinine dipstick results and those by a standard rate-Jaffe cuvet method for creatinine. DISCUSSION: With the simultaneous measurement of creatinine and albumin in urine, the albumin/creatinine ratio can be determined effectively reducing or eliminating the occasional false-negative and false-positive result in those with dilute or concentrated urines, respectively. The dipstick test for these analytes permits the simple identification of individuals with possible albuminuria and could serve well in a point-of-care setting.

Left-hemisphere activation and deficient response modulation in psychopaths.

Psychopathic offenders have difficulty processing contextual or secondary cues once they have initiated goal-directed behavior or allocated attention to a primary task. To test the hypothesis that this deficit in response modulation is specific to conditions in which psychopaths' left-hemisphere resources are engaged, we administered a serial recall task to 21 incarcerated psychopaths and 21 control subjects. Subjects were instructed to memorize eight words that were presented one at a time, each in one of the four corners of the visual display. Subjects' primary task was to recall the words in serial order. Then, without forewarning, they were asked to recall the words' locations. As predicted, psychopaths performed as well as control subjects in recalling words from the left and right spatial fields, but recalled significantly fewer locations from the right spatial field. Thus, psychopaths' deficient response modulation was specific to conditions in which their left-hemisphere resources were actively engaged.

Comparison of urine dipsticks with quantitative methods for microalbuminuria.

We describe a new dip- and read dipstick that detects urine albumin at concentrations of 10 mg/l and above and urine creatinine at concentrations of 300 mg/l and above. The albumin assay is based on a high-affinity, dye-binding technique while the creatinine assay is based on the peroxidase-like activity of copper creatinine complexes. With these two-test dipsticks, urines from normal adults supplemented with albumin and creatinine were correctly identified to within +/- 15% of the expected value for both analytes; the between-day coefficients of variation ranged from 7.1% to 16.1%. We tested 275 patients' unmodified urines by the Bayer and Boehringer Mannheim Micral-Test albumin dipsticks and for albumin with the Beckman Array on the same specimens. We also analyzed 42 selected urines from the group of 275 for albumin by another quantitative immunochemical method and by electrophoresis plus a total protein method to estimate the albumin concentration. The quantitative immunochemical methods appear to underestimate the urine albumin concentrations; in these 42 urines measured as negative, i.e., < ca. 16-20 mg/l, by one of the quantitative method but positive by the Bayer dipstick, 33 of these were positive by the electrophoresis/total protein assay combination. The Bayer albumin dipstick correctly identified urines as having < 16 mg/l or > or = 16 mg/l at an 80% rate. At a cutoff of 20 mg/l, the rate increased to 87%. We also determined the urinary albumin/creatinine ratios on the 275 patients using the Bayer two-pad dipstick and found agreement 84% of the time with the same ratio obtained from a quantitative immunochemical method for albumin and a rate-Jaffe method for creatinine; an albumin/creatinine ratio (mg/g) of 30 was used as the discrimination point. Albumin stability studies performed on the Beckman Array patients with six fresh urines showed small but consistent decreases at -20 degrees C but not at 4 degrees C after one month of storage. The albumin in contrived urines, as estimated by electrophoreses/total protein and by the dipsticks did not change at these storage conditions. Boric acid at 1 g/l as a urine preservative had no effect on the measurement of albumin by any of the methods described here nor of the assay of creatinine. Other urinary proteins present at abnormal excretion rates did not interfere with the Bayer albumin dipstick. Abnormal concentrations of bilirubin, citrate, creatine, ascorbic acid, albumin, hemoglobin and myoglobin in urine did not interfere with the creatinine dipstick measurements. The first four of the above did not affect the Bayer dipstick results for albumin.

A fourth year of training in ambulatory medicine: the University of Washington experience.

Postresidency training in ambulatory general internal medicine has been proposed as a means to enhance the generalist skills of internal medicine graduates. At the University of Washington, a fourth year of training in ambulatory medicine has been offered since 1967. The resident training year provides a core experience in general internal medicine as well as the opportunity for elective experiences in subspecialties and other allied specialties. Graduates of this year of experience in ambulatory training were surveyed to determine current practice patterns and retrospective evaluation of the program; responses were received from 36 of 52 graduates (69%). Among respondents, 50% are general internists, 39% subspecialists, and 11% in other practice specialties. Eight respondents (22%) are practicing in rural communities. Respondents identified the specialized training in outpatient medicine as the primary strength of the additional training year. Many reported using the year to gain additional training tailored to their future practice. The fourth year of ambulatory training thus represents an efficient means to provide additional training to internists planning careers in general internal medicine. It can serve a variety of purposes, including preparation for practice in rural and other settings with unique clinical demands, training of clinician educators, and retraining of subspecialists seeking to shift to generalist practice.

Effects of motivationally significant stimuli on the regulation of dominant responses.

In 4 experiments, Ss responded as quickly as possible to indicate whether character strings consisted of letters or numbers. Following a warning stimulus that was or was not designed to trigger a motivational-emotional response in particular subgroups (viz., those with high anxiety, discrepant self-concepts, and eating disorders), strings were presented in a central (dominant) location on 75% of the trials or in 1 of 4 peripheral (nondominant) locations. Consistent with hypotheses, response times to peripherally located strings were significantly slower following motivationally significant than following neutral warning stimuli. Contrary to hypotheses, such stimuli did not facilitate responding to centrally located strings. It is proposed that motivationally significant stimuli engender a temporary reduction in control processing that hinders regulation of dominant responses.

An evaluation of the efficacy of cordial for preventing post-weaning diarrhoea in pigs.

An evaluation of the efficacy of a commercial crystalline cordial concentrate for preventing post-weaning diarrhoea (PWD) and improving weight gains in pigs following weaning, was carried out in 3 herds using 861 pigs. The incidence of PWD in pigs drinking the cordial was reduced in 2 herds and its severity was reduced in one of these. There was no effect on either incidence or severity in the other herd. The pigs given cordial consumed considerably more water per day and less feed per day than pigs drinking plain water during the 10-day supplementation period. There was no improvement in average daily gain or feed conversion ratio attributable to adding cordial to drinking water in any of the herds. In one herd the growth rate of pigs receiving cordial was actually depressed during the supplementation period. There was no reduction in mortality or in number of treatments given for diarrhoea in pigs receiving cordial.

Man's Closest Companions.

THE AUTHORS DESCRIBE FOUR COMMON PARASITES THAT INFEST HUMANS: the head louse, the pubic louse, and the body louse, as well as the human mite. They review the life cycle of these insects, advise on diagnosis of an infestation, and recommend various types of treatment for their human hosts that will put an end to these unwelcome pests.

Restructuring an internal medicine residency program to meet regional and national needs for general internists.

The Department of Medicine at the University of Washington has reorganized its residency program to increase the emphasis on general internal medicine and primary care. New teaching services in community hospitals have been established, clinical training sites in Montana, Idaho and Eastern Washington opened, and primary care residency tracks begun. Current data indicate that a major shift in the career plans of our new residents also has occurred. Whereas a decade ago approximately two thirds of our residents were becoming subspecialists, almost two thirds of our 1979 and 1980 program graduates are headed towards careers as general internists. Many will practice in the region's smaller cities and towns. The program serves as a model for the development of a regional program for graduate training in internal medicine.

Amoxicillin, a new penicillin antibiotic.

Amoxicillin (alpha-amino-p-hydroxybenzyl penicillin, BRL 2333) is a new semisynthetic penicillin which is structurally similar to ampicillin, but which is better absorbed and yields higher concentrations in serum and urine. The in vitro susceptibility of 145 strains of Enterobacteriaceae and 30 isolates of Pseudomonas aeruginosa was determined against various concentrations of amoxicillin and ampicillin in agar. In addition, inhibitory zones around discs containing 10 mug of amoxicillin were measured and compared with results of agar dilution studies. The drug also was evaluated in the treatment of 38 patients with bacteriuria, who received doses of either 750 mg or 1 g/day for 10 days. In vitro, amoxicillin was comparable in activity to ampicillin; most isolates of Escherichia coli and Proteus mirabilis were inhibited by 10 mug or less/ml, whereas the majority of strains of Enterobacter, Klebsiella, indole-positive Proteus species, and Pseudomonas grew in concentrations greater than 50 mug/ml. Clinically, amoxicillin was effective in eradicating bacteriuria due to susceptible organisms and was very well tolerated. For practical purposes, however, amoxicillin performed no better than a host of other drugs presently available for the treatment of acute, uncomplicated bacteriuria.