Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1998-04-23
2001-04-24
Navarro, Albert (Department: 1645)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007920, C436S501000, C436S518000, C436S548000
Reexamination Certificate
active
06221611
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the use of ABP as a prognostic and diagnostic indicator. Specifically, the level of ABP in the urine is measured. An increased level of AEP measured on hospital arrival indicates the presence of serious systemic infection, and also indicates an increased chance of mortality during hospitalization. ABP measurement in the urine can be used either alone or in conjunction with other known tests to determine mortality.
BACKGROUND OF THE INVENTION
Adenosine deaminase binding protein (referred to herein as “ABP”) is a 120,000 dalton surface glycoprotein found on the brush border of the kidney proximal tubular epithelial cell. In addition to the proximal tubule, ABP has been detected in human prostate tissue, skin, renal medulla and mucosa of the intestinal tract. Smaller amounts have been detected in the liver, lung, pancreas and endometrial tissue.
ABP is released in the urine when the proximal tubule of the kidney is affected. ABP has therefore been used as a marker for acute renal injury (Thompson et al., Toxicol. Pathol., Vol. 14, p. 232-237 (1986)). For example, ABP is released in high concentrations in the urine in patients with acute renal tubular necrosis (Goren, et al., Am J. Clin. Pathol., Vol. 86, p. 780-783 (1986)). In addition, patients with renal transplant rejection have high concentrations of ABP in the urine (Tolkoff-Rubin, et al., Transplantation, Vol. 41, p. 593-597 (1986)). High levels of ABP are not found in patients with glomerular disease, prerenal azotemia, or in healthy controls (Tolkoff-Rubin, Kidney International, Vol. 29, p. 142-152 (1986)).
Other proteins have been used as indicators of renal disease. These include N-acetyl-&bgr;-D-glucosaminidase, b2-microglobulin and microsomal aminopeptidase (see Vanderlinde, Ann. Clin. Lab. Sci., Vol. 11, 189-201 (1981) and Price, Toxicoloy, Vol. 23, p. 99-134 (1982)). However, clinical use of these markers is limited as they are not disease- or condition- specific. Further, these proteins are unstable in urine, and are subject to enzyme inhibitors and other interfering substances in the urine.
The inventor of the instant application has determined that high levels of ABP in the urine can be used as a prognostic indicator for mortality and as a diagnostic indicator for sepsis, or serious systemic infection. ABP is measured in the urine utilizing an ELISA technique. It has been determined that ABP concentrations are elevated with several acute medical illnesses. These include illnesses caused by infectious diseases, usually caused by bacteria. In addition, patients with high levels of ABP in the urine have increased mortality as compared with individuals having normal ABP levels in the urine. Hence, ABP urine measure is a marker for serious systemic infection and for certain types of acute illness, and is also a marker for increased mortality.
Prior here to, clinicians have relied on certain symptoms, signs and objective measures to determine severity of illness. For example, clinicians have used an altered mental status, decreased urine output, high pulse rate, high respiratory rate and/or decreased blood pressure to indicate the presence of a systemic process that is significantly effecting a patient's health. However, these variables only reflect biochemical changes that occur in the body. If one can detect the substances that are released in response to insult to the body, which substances are found before the physiological abnormalities described, then one can treat the causative disease at earlier stages, as once an infection leads to sepsis, mortality rates range from 50-75%. Also, it may be difficult to distinguish a relatively benign condition from a more serious illness at the earliest stages, as clinically they may appear to be similar. The marker described herein, ABP, can be used as part of the clinicians judgment, alone or in conjunction with other objective tests and severity of illness scales, to identify patients with more significant illness.
SUMMARY OF THE INVENTION
This invention is directed to a method of diagnosing serious systemic infection. Such infections include, but are not limited to, pneumonia, cellulitis, gastroenteritis, pyelonephritis and joint infection. Serious systemic infection is diagnosed in a subject by measuring the level of ABP in the urine of said subject. An increased ABP level indicates an increased likelihood of a positive diagnosis.
This invention is further directed to a method of determining an increased chance of mortality in a subject. The level of ABP in the urine of a subject is measured. An increased level of ABP in the urine indicates an increased chance of mortality. This test can be combined with other known tests, such as APACHE II, SAPS II or MPM, to determine an increased chance of mortality in a subject.
REFERENCES:
patent: 4731326 (1988-03-01), Thompson et al.
Westhuyzen et al (Clinica Chimica Acta vol. 228 pp 123-132, 1994.*
Tolkoff—Rubin et al. Nephro. Dial. Transplant 2:143-148, 1987.*
Thompson et al. Clin. Chem 31(5):679-683, 1985.*
Cerra et al. Arch. Surg. 125:519-522, 1990.*
Lemeshow et al. JAMA 270(20):2478-2485, 1993.
Fulbright & Jaworski LLP
Navarro Albert
Signet Laboratories, Inc.
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