Electrically injected VCSEL with a composite DBR and MHCG reflector.

We achieve the continuous-wave (CW) lasing of electrically-injected, first-of-their-kind vertical-cavity surface-emitting lasers (VCSELs) that use a subwavelength monolithic high-refractive-index-contrast grating (MHCG) mirror. The MHCG, unlike the well-known high-refractive-index-contrast grating (HCG) is neither a membrane suspended in the air nor a structure that requires a cladding layer. The MHCG is patterned in a semiconductor material atop the VCSEL cavity creating an all-semiconductor laser. Static measurements show CW operation of the VCSELs from room temperature up to 75 °C. The VCSEL with a 13.5 µm current oxide aperture diameter operates with quasi-single mode emission from threshold to rollover. Our results open a way to produce all-semiconductor surface emitting lasers emitting at wavelengths from the ultraviolet and the visible (GaN-based) to the infrared (InP- and GaSb-based) with a reduced vertical thickness and thus we believe the manufacturing costs potentially will be reduced by approximately up to about 90% in comparison to the typical DBR VCSELs. Our VCSELs have immediate and emerging applications in optical communication, illumination, sensing, and as light sources in photonic integrated circuits.

Gigahertz modulation of GaAs-based bipolar cascade vertical cavity surface-emitting lasers.

The high-frequency modulation characteristics of GaAs-based bipolar cascade vertical cavity surface-emitting lasers operating at 980 nm with GaAs tunnel junctions and p-doped Al0.98Ga0.02As oxide apertures have been measured. We achieve -3 dB laser output modulations of 6.5 GHz for two-stage and 9.4 GHz for three-stage devices in response to small-signal current injection at an operating temperature of -50 degrees C.

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.

Prolonged hyperlipasemia attributable to a novel type of macrolipase.

BACKGROUND: We present the case of an 80-year-old woman who was admitted to hospital with an intermittent volvulus of the right colon. A total colectomy was performed. Initially, serum amylase and lipase increased concordantly, but after a few weeks amylase normalized (85 U/L), whereas lipase increased to 3764 U/L. This discrepancy and persistence of hyperlipasemia suggested a macromolecular form of lipase. METHODS: The nature of the macromolecular complex was studied using high-pressure liquid gel-permeation chromatography, affinity chromatography, (immuno)electrophoresis, and immunodiffusion. RESULTS: Gel-permeation chromatography revealed a macrolipase, with a molecular mass >900 kDa, that contributed up to 56% of total serum lipase activity. Butanol extraction of the specimen did not alter the elution profile. The thermostabilities of pancreatic lipase and the macroform were similar, whereas activation energy (E:(a)) was lower in the macromolecular lipase (28 +/- 4 kJ. mol(-1). K(-1) vs 48 +/- 7 kJ. mol(-1). K(-1) (P: = 0.02). Agarose electrophoresis showed a broad band of lipase activity at the application site. Protein A-Sepharose affinity gel chromatography excluded IgG-linked lipase. Agarose electrophoresis and immunofixation excluded linkage to other immunoglobulins. Radial immunodiffusion did not show lipase activity in the immunoglobulin precipitation bands. Radial immunodiffusion with alpha(2)-macroglobulin (alpha(2)-MG) antibodies showed a diffuse spot of lipase activity within the precipitation band, suggesting a macromolecular association between lipase and alpha(2)-MG. Affinity gel chromatography against alpha(2)-MG showed lipase activity in the alpha(2)-MG-bound fractions. CONCLUSION: This is the first report of a macrolipase in which an association between alpha(2)-MG and lipase is described.

Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests.

PURPOSE: To review information on performance characteristics for tests that are commonly used to identify acute and chronic hepatic injury. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed for key words related to hepatic tests, including quality specifications, aminotransferases, alkaline phosphatase, gamma-glutamyltransferase, bilirubin, albumin, ammonia, and viral markers. Abstracts were reviewed, and articles discussing performance of laboratory tests were selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. The drafts were also reviewed by the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and approved by the committee and the Association's Council. RECOMMENDATIONS: Although many specific recommendations are made in the guidelines, some summary recommendations are discussed here. Alanine aminotransferase is the most important test for recognition of acute and chronic hepatic injury. Performance goals should aim for total error of <10% at the upper reference limit to meet clinical needs in monitoring patients with chronic hepatic injury. Laboratories should have age-adjusted reference limits for enzymes in children, and gender-adjusted reference limits for aminotransferases, gamma-glutamyltransferase, and total bilirubin in adults. The international normalized ratio should not be the sole method for reporting results of prothrombin time in liver disease; additional research is needed to determine the reporting mechanism that best correlates with functional impairment. Harmonization is needed for alanine aminotransferase activity, and improved standardization for hepatitis C viral RNA measurements.

Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring.

PURPOSE: To review information on the use of laboratory tests in screening, diagnosis, and monitoring of acute and chronic hepatic injury. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed for key words related to hepatic diseases, including acute hepatitis, chronic hepatitis, alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, and etiologic causes. Abstracts were reviewed, and articles discussing use of laboratory tests selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. RECOMMENDATIONS: Although many specific recommendations are made in the guidelines, only some summary recommendations are listed here. In acute hepatic injury, prothrombin time and, to a lesser extent, total bilirubin are the best indicators of severity of disease. Although ALT is useful for detecting acute and chronic hepatic injury, it is not related to severity of acute hepatic injury and only weakly related to severity of chronic hepatic injury. Specific tests of viral markers should be the initial differential tests in both acute and chronic hepatic injury; when positive, they are also useful for monitoring recovery from hepatitis B and C.

Use of continuous quality improvement to identify barriers in the management of hypertension.

We have made great strides in understanding the pathophysiology and medical management of hypertension, yet barriers to effective blood pressure control remain. The process of identifying the barriers within the health care system may be as important as the barriers themselves. Our primary purpose was to apply the widely accepted tool, Continuous Quality Improvement (CQI), to identify barriers to the management of hypertension. We wanted to identify the most important factors and (or) persons in effective blood pressure control and to compare costs, satisfaction, and blood pressure control among subgroups of patients to identify those most likely to benefit from interventions. We recruited patients with essential hypertension who came to a university-based clinic staffed by family physicians and residents; 181 patients with hypertension were identified and asked at the time of their visit to complete a questionnaire relating to the management of their blood pressure. Twenty-five physicians and 8 medical assistants were also asked to complete a similar questionnaire regarding their perceptions of barriers to blood pressure management. All other information came from the patients' medical records. Blood pressure control was based on a reading taken on the date the questionnaire was completed. Student's t test was used to determine if statistically significant differences existed in blood pressure control, patient satisfaction, and total costs for certain subgroups; regression analysis was used to determine correlations. We had completed questionnaires from 91 patients, 89 physicians, and 79 staff. The physicians and staff were of course involved; however, we found that the patients' gestalt was extremely important in blood pressure control. Our patients perceived that lifestyle modifications such as exercise and weight loss were the greatest barrier to better blood pressure control. The cost of certain antihypertensive drugs was an obstacle for some patients. African Americans had poorer blood pressure control, and their satisfaction of care was significantly lower than that of other races. Our patients taught us that the 2 major barriers to blood pressure control were changes in lifestyle and reducing the cost of medications. We also found that our African American patients showed the poorest blood pressure control and the greatest dissatisfaction with their care. We surmise that the greatest benefit of any intervention would be expected in this population. We demonstrated that CQI can be used to identify barriers to hypertension management and subgroups of patients likely to benefit from interventions.

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.

Screening for proteinuria in Japanese schoolchildren: a new approach.

By governmental mandate, Japanese school children are screened annually for proteinuria, hematuria, and glucosuria to identify children with possible renal disorders. We added urine dipstick tests for albumin and creatinine to the Japanese screening protocol, and used their dipstick results for blood, glucose and protein. The sulfosalicylic acid precipitation test was used to confirm "trace" positive protein dipsticks. The Japanese and our screening protocol have in common the same data for glucosuria and proteinuria. Their scheme has an algorithm for repeat testing of children with abnormal results, and further testing and medical evaluation for those showing persistently abnormal values. Out of the 23,121 students, we found seven with likely nephritis, one with confirmed nephritis, one with nephrotic syndrome, 170 with persistent unexplained hematuria, 19 with persistent unexplained proteinuria, 14 cases of urinary tract infection, and 20 cases of likely diabetes mellitus. We conclude that dipstick testing for albumin, protein, creatinine, glucose and occult blood has significant value in a multilevel testing scheme for identifying children with urinary tract abnormalities or diabetes. The assay of albumin increases the sensitivity of the screening, and dividing the albumin by the creatinine concentration reduces the potential errors arising from concentrated or dilute urines.

High-sensitivity dye binding assay for albumin in urine.

We developed a dye-binding method for albumin in urine based on bis (3',3"-diiodo4'4"-dihydroxy-5'5"-dinitrophenyl)-3,4,5,6-tetrabr omosulfonphthalein (DIDNTB), a dye that has a higher chemical sensitivity and specificity for albumin when compared to two other commonly used dyes. We prepared urine dipsticks with DIDNTB and certain other compounds to prevent "nonspecific" binding to the dipstick matrix. The detection limit for albumin with DIDNTB as the dye is about 10 mg/L. The extent of dye binding to proteins and other compounds was studied using ultracentrifugation and a selectively permeable membrane that permitted the passage of free but not bound dye; we believe this method is superior to photometric titration. The affinity of the dyes for albumin was found to be pH dependent with stronger binding at pH 1.8 than at pH 7.0. At pH 1.8, DIDNTB had a ca.10-fold greater binding coefficient to albumin when compared to the widely used dyes, tetrabromophenol blue (CI 4430-25-5) or bromophenol blue (CI 115-39-9). We developed a system that minimized nonspecific binding by the dye through the use of polymethyl vinyl ethers and bis-(heptapropylene glycol) carbonate. DIDNTB showed a greater chemical specificity for albumin when compared to most other proteins. The new albumin dipsticks are resistant to many potential interferences at substantial concentrations, making the dipsticks suitable to screen for albuminuria.

Screening school children for albuminuria, proteinuria and occult blood with dipsticks.

Beginning in 1974, the Japanese Ministry of Health Welfare directed the screening of schoolchildren for proteinuria. We studied their procedure and methods in 6197 school children and also evaluated a new urine dipstick that measures albumin concentrations down to about 10 mg/l and creatinine down to about 300 mg/l. We used specimens from adult in- and outpatients to test the accuracy of the dipsticks. Based on the quantitative results, we set as cutoffs < 150 mg/l for protein and < 30 mg/l for albumin as the concentrations representing "low risk." The quantitative values were assumed to be correct, and the dipstick results were judged accordingly, i.e., a dipstick protein of > or = "150" mg/l or an albumin of I "30" mg/l indicated increased risk of developing or having a genitourinary disorder. The sensitivity/specificity of the protein dipstick was 95.1%/95.5%, and the same for the albumin dipstick was 83.8%/93.8%. The cut-off for the albumin dipsticks probably should be set somewhat lower to reduce the number of false negatives and increase the sensitivity of the dipstick. When we compared the quantitative albumin to the protein dipsticks with the above cut-offs, we found the sensitivity/specificity to be 79.3%/94.4%, i.e., much like the albumin dipstick results. The many reports on the association of albuminuria and risk of renal disease recommend that screening should be done for albumin rather than protein. Based on the data from the school children, we estimate that a dipstick albumin of "30" mg/l is borderline increased risk, and that a protein dipstick of "150" mg/l is the same. If we call the dipstick "10" mg/l albumin, "30" mg/l albumin and the "150" mg/l protein results "low risk," then we estimate the prevalence of albuminuria in the school children to be about 2.1% and proteinuria to be about 4.3%. Children with these values should have a quantitative test for albumin and protein. We also tested a dipstick for creatinine and found increasing values with increasing age in both genders; the older boys had significantly higher creatinine values than the older girls and younger boys. For the albumin/creatinine ratio, we found 6028 children with a ratio of < 30 mg/g indicating low risk and 159 children with a ratio of > or = 30 mg/g indicating increased risk. The ratio may be more useful owing to the likely reduction of the number of false negatives and false positives.

Setting process control limits for enzyme tests in serum.

With the advent of much more precise laboratory equipment, the use of performance-based standard deviations for enzymes, e.g. those based on the precision of the laboratory during a period of "satisfactory performance", is not appropriate; it leads to overly rigid precision limits and unnecessary repeat assays, and is wasteful of resources. Testing for the commonly used serum enzymes does not require tight precision given how enzyme data are viewed by most clinicians. Other ways to set process control limits all have some arbitrary content; however, this need not prevent their use. Laboratorians must choose the approach that is appropriate for their laboratory and medical staff to meet medically perceived needs.

Comparison of instrument-read dipsticks for albumin and creatinine in urine with visual results and quantitative methods.

Three hospital sites evaluated the Bayer two-pad urine dipstick as a screening test for microalbuminuria. One pad estimates albumin concentrations between 10 and 150 mg/L, and the second estimates creatinine values between 300 and 3,000 mg/L. The Boehringer Mannheim (BMD) Micral dipstick was also compared and evaluated. The accuracy of the dipsticks was judged by comparison with cuvet-based immunonephelometry for albumin and to standard rate-Jaffe methods for creatinine; these assays were well standardized and controlled and were assumed to give accurate values. Precision of these methods and that of the dipsticks was determined by multiple assays of control materials. Visual or instrument (Clinitek 50 or 100) evaluation of the Bayer or visual checks of the BMD albumin dipstick pad with patients' urines gave clinically acceptable accuracy. The albumin/creatinine ratio from the Bayer dipsticks gave better accuracy for albumin excretion than the albumin pads alone from either manufacturer. This ratio should permit making a good estimate of the 24-hr albumin excretion in a randomly collected urine.

Reported alcohol consumption and the serum carbohydrate-deficient transferrin test in third-year medical students.

The serum carbohydrate-deficient transferrin (CDT) test was performed on 143 third-year medical students along with questionnaires for the self-reporting of alcohol consumption during the last 2 weeks, the last 6 months, and questions on any alcohol-related untoward events. We found that the CDT test has poor sensitivity for detecting binge drinking in our population of students, despite some likely under-reporting of drinking. Self-reporting of drinking is commonly unreliable, and we found no significant correlation between the CDT concentrations in serum and the magnitude of self-reported alcohol use during 2-week and 6-month periods. Hangover was by far the commonest self-reported untoward event, and there was a highly significant relationship (P < 0.001) between drinking and untoward events. From a small population of non-drinkers, we estimated the reference ranges for CDT to be <27 U/l for men and <35 U/l for women.

Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.

OBJECTIVE AND DESIGN: 1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain. MATERIALS AND METHODS: The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin. RESULTS: CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity. CONCLUSIONS: CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.

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.

Increased alkaline phosphatase isoforms in autoimmune diseases.

We found significant increases in ALP and ALP isoform band 10 in the serum of patients with early insulin-dependent diabetes, rheumatoid arthritis, and in those with multiple sclerosis during periods of disease exacerbation as compared with healthy controls. The ALP isoforms were assayed by isoelectric focusing. Our data suggest that the increase in ALP and ALP-10 closely reflects the abnormal activation of T lymphocytes that is common in autoimmune diseases, and that the source of the ALP-10 is activated T lymphocytes. ALP-10 is a sensitive but nonspecific marker of an active autoimmune process and appears to have the ability to detect abnormal T-cell activation. ALP-10 may be a useful test in the screening for autoimmune disorders.