Method for identifying and monitoring patients at risk for systemic inflammatory conditions and apparatus for use in this method

• US 6,190,872 B1
• Filed: 08/25/1998
• Issued: 02/20/2001
• Est. Priority Date: 05/06/1994
• Status: Expired due to Term

• Current Assignee: Gus J. Slotman
• Original Assignee: Gus J. Slotman
• Inventors: Slotman, Gus J.
• Primary Examiner(s): Minnifield, Nita
• Assistant Examiner(s): BASKAR, PADMAVATHI
• Application Number:
  US09/139,189
• Time in Patent Office: 910 Days
• Field of Search: 435/34, 435/7.32, 435/7.24, 435/7.29, 435/7.92, 435/69.4, 435/172.3, 514/2, 514/12, 514/8
• US Class Current: 435/7.92
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/88 involving prostaglandins or their receptors

Abstract

A method of identifying and monitoring patients at risk for developing a systemic inflammatory condition prior to development of signs and symptoms using a systemic mediator-associated physiologic test profile is provided.

Claims

1. A method of identifying a patient at risk for developing a selected systemic inflammatory condition prior to development of signs and symptoms which are diagnostic of the selected systemic inflammatory condition comprising;

a) measuring selected physiological parameters in the patient, wherein measured selected physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6-keto F1α

, thromboxane B₂, leukotrienes B₄, C₄, D₄ and E₄, interleukin 1β

, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;

b) producing a systemic mediators-associated response test profile for the patient, wherein said systemic mediators-associated response test profile comprises the physiological parameters set forth in step (a); and

c) comparing said profile with an established control profile to identify the patient as being at risk for developing a selected systemic inflammatory condition prior to development of signs and symptoms which are diagnostic of the selected systemic inflammatory condition wherein the systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma.

2. A method of identifying a patient at risk for developing a selected systemic inflammatory condition prior to development of signs and symptoms which are diagnostic of the selected systemic inflammatory condition comprising:

a) measuring selected physiological parameters in the patient, wherein measured selected, physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6-keto F1α

, thromboxane B₂, leukotrienes B₄, C₄, D₄ and E₄, interleukin 1β

, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;

b) producing a systemic mediators-associated response test profile for the patient, wherein said systemic mediators-associated response test profile comprises the physiological parameters as set forth in step (a); and

c) comparing said profile with an established control profile to identify the patient as being at risk for developing a selected systemic inflammatory condition prior to development of signs and symptoms which are diagnostic of the selected systemic inflammatory condition wherein the systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma, wherein concentrations at acute inflammatory response mediators are measured simultaneously via enzyme linked immunosorbent assays in a multiple analysis grid for grouped independent enzyme linked immunosorbent assays comprising;

an antibody grid;

a reagent grid placed on top of said antibody grid; and

an injection grid placed on top of said reagent grid.

3. A method of quantitatively predicting selected physiological parameters in a patient having or at risk for a selected systemic inflammatory condition comprising:

a) measuring selected physiological parameters in said patient, wherein measured selected physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6keto F1α

, thromboxane B₂, leukotrienes B₄, C₄, D₄ and E₄, interleukin-1β

, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;

b) producing a systemic mediators-associated response test profile for said patient, wherein said systemic mediators-associated response-test profile comprises the physiological parameters as set forth in step (a); and

c) comparing said profile with an established control profile from multiple patients with systemic inflammatory disease so that selected physiological parameters in said patient having or at risk for a selected systemic inflammatory condition are determined wherein the selected systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma.

4. A method of quantitatively predicting selected physiological parameters in a patient having or at risk for a selected systemic inflammatory condition comprising:

a) measuring selected physiological parameters in said patient, wherein measured selected physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6-keto F1α

, thromboxane B₂, leukotrienes B₄, C₄, D₄ and E₄, interleukin 1β

, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;

b) producing a systemic mediators-associated response test profile for said patient, wherein said systemic mediators-associated response test profile comprises the physiological parameters as set forth in step (a); and

c) comparing said profile with an established control profile from multiple patients with systemic inflammatory disease so that selected physiological parameters in said patient having or at risk for a selected systemic inflammatory condition are determined wherein the selected systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma, wherein concentrations of acute inflammatory response mediators are measured simultaneously via enzyme linked immunosorbent assays in a multiple analysis grid for grouped independent enzyme linked immunosorbent assays comprising;

an antibody grid;

a reagent grid placed on top of said antibody grid; and

an injection grid placed on top of said reagent grid.

5. A method of monitoring changes in selected physiological parameters in a patient to assess a treatment of a systemic inflammatory condition comprising:

a) measuring selected physiologic parameters in a patient, wherein measured selected physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6keto F1α

, thromboxane B₂, leukotrienes B₄, C₄, D₄ and E₄, interleukin 1β

, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;

b) producing a systemic mediators-associated response test profile for the patient, wherein said systemic mediators-associated response test profile comprises the physiological parameters as set forth in step (a);

c) monitoring changes in the measurements in said profile; and

d) comparing changes in said profile with an established control profile to monitor treatment of a systemic inflammatory condition wherein the systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma.

6. A method of Monitoring changes in selected physiological parameters in a patient to assess a treatment of a systemic inflammatory condition comprising:

a) measuring selected physiologic parameters in a patient, wherein measured selected physiologic parameters comprise physical examination, vital signs, hemodynamic measurements and calculations, clinical laboratory tests and concentrations of acute inflammatory response mediators, wherein said acute inflammatory response mediators comprise prostaglandin 6-keto F1α

, thromboxane B₂, leukotrienes B₄, C₄, D₄ and E₄, interleukin 1β

, interleukin-6, interleukin-8, tumor necrosis factor, neutrophil elastase, complements C3a and C5a, platelet activating factor, nitric oxide metabolites and endotoxin levels;

b) producing a systemic mediators-associated response test profile for the patient, wherein said systemic mediators-associated response test profile comprises the physiological parameters as set forth in step (a);

c) monitoring changes in the measurements in said profile; and

d) comparing changes in said profile with an established control profile to monitor treatment of a systemic inflammatory condition wherein the systemic inflammatory condition is selected from a group consisting of Adult Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, sepsis, Multiple Organ Dysfunction Syndrome, single organ dysfunction, shock, transplant rejection, cancer and trauma, wherein concentrations of acute inflammatory response mediators are measured simultaneously via enzyme linked immunosorbent assays in a multiple analysis grid for grouped independent enzyme linked immunosorbent assays comprising wherein the enzyme linked immunosorbent assays are performed using a multiple analysis grid for grouped independent enzyme linked immunosorbent assays comprising;

(a) an antibody grid;

(b) a reagent grid placed on top of said antibody grid; and

(c) an injection grid placed on top of said reagent grid.