RU2280865C1 - Express diagnosis method for diagnosing endogenous intoxication cases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves placing blood serum drops on object-plates. Each drop is covered with micro glasses and dried at t= 20-24°C during 1-1.5 h and held on open air during 1.5-2 h. Then, the samples are studied with microscope in passing light, polarized light and n polarized light with quartz compensator. When studying a preparation in passing light with crystals found therein: (and/or) skeletal, stepped, nodular fibrils and rectangular branched aggregates, hyperglobulinemia is to be diagnosed. When studying a preparation in polarized light with optically active crystals like radial radiant spheroliths being detected, hypercholesterolemia is to be diagnosed; needle-like crystals being found, hyperuricemy is to be diagnosed; branching dendrites being found, hypercreatinemia is to be diagnosed. When studying a preparation in polarized light with quartz compensator and multi-colored crystals being observed: (and/or) - plates, fan-like plates being found, hyperputrescinemia is to be diagnosed; ovoid grains being observed, hyperphenylalaninemia is to be diagnosed; (and/or)- druses, polyheders and prisms being observed, hyperhistidinemia is to be diagnosed; chain-oriented aggregates from grains being found, hypertriptophanemia is to be diagnosed; grain aggregates being found, hyperbilirubinemia is to be diagnosed.

EFFECT: high information capacity; enhanced effectiveness in visually checking selective endotoxicosis markers; wide range of functional applications.

20 dwg

Description

The present invention relates to medicine: surgery, gynecology, resuscitation, endocrinology, traumatology, dentistry; biology, biophysics and can be used for rapid diagnosis of situational endogenous toxemia.

Endotoxicosis is a complex multifactor autocatalytic process that, over time, acquires a universal character, depending on the mechanisms that launched it. Unbalanced biologically active substances that acquire the properties of endogenous toxic substances (ETS) become damaging agents.

The components of the syndrome: toxemia, the concentration of circulating ETS, both received from the primary focus and those that arose a second time as a result of tissue damage, are a manifestation of an aggression factor (I. Yerukhin, B.V. Shamkov, Endotoxicosis in a surgical clinic. S.-P. - 1995. Leontiev N.V., Belotserkovsky M.V. Syndrome of endogenous intoxication. - S.P. - 1998. - St. Petersburg State Medical University).

Endogenous intoxication of the body is associated with many diseases and often serves as the main cause of deaths. Along with the specific features inherent in one or another nosological form of the disease, occurring with endotoxemia syndrome have many common biochemical and pathophysiological mechanisms. The prognosis of the disease, as well as the degree of violation of homeostatic constants of the body in individual individuals, largely depends on the type of metabolic distress (Belyakov N.A., Malakhova M.Ya. Criteria and diagnosis of endogenous intoxication // In Sat. Endogenous intoxication. St. Petersburg. , 1994, S. 60-62; Clin. Honey. - 1981. - No. 10 (38).

Severe endogenous intoxication, as a rule, accompanies chronic diseases of the liver, kidneys, pancreas, burn toxicosis, peritonitis, acute intestinal obstruction, sepsis, extensive injuries, gynecological diseases, etc.

Most of these conditions are characterized by: hyperbilirubinemia, hyperglobulinemia, impaired synthesis of proteins, amino acids due to impaired synthetic, detoxification function of the liver; with the accumulation of products of nitrogen metabolism (creatinine, uric acid) that occurs with blockade of kidney function; with peritonitis, burn disease, putrefactive processes, polyamines (biogenic amines - cadaverine, putrescine) predominate, which are the products of protein biodegradation (Dorokhin K.M., Spas V.V. Pathophysiological aspects of endogenous intoxication syndrome // Anesthesiology and Renimatology. - 1994. - No. 1. - P. 56-60; Dean R. Decay processes in a cell. M., 1981; Lopukhin Yu.M., Molodenkov MN. Hemosorption. M., 1985; Kishkun A.A., Kudinova A. S., Ofitova, A.D., Mishurina, R.B., The value of secondary molecules in assessing the level of endogenous intoxication, Military Medical Journal. - 1996. - No. 2, - p. 41-44).

An increase in the fraction of α-1-globulins is observed in acute, subacute, exacerbation of chronic inflammatory processes; damage to the liver, all processes of tissue decay or cell proliferation.

An increase in the fraction of α-2-globulins is observed in all types of acute inflammatory processes, especially with a pronounced exudative and purulent character (pneumonia, pleural empyema, other types of purulent processes), autoimmune diseases; malignant tumors; in the recovery stage after thermal burns; nephrotic syndrome.

The growth of β-globulin fractions is detected in liver diseases, primary and secondary hyperlipoproteinemia, hypothyroidism, diabetes mellitus, and nephrotic syndrome.

An increase in the content of γ-globulins containing immunoglobulins G, A, M, D, E is noted during the reaction of the immune system, when antibodies and autoantigens are produced: for viral and bacterial infections, inflammation, tissue destruction, burns; with hepatitis and cirrhosis; hemoblastosis, candidomycosis; SLE (Nazarenko G.I., Kishkun A.A. Clinical evaluation of the results of laboratory studies. M., 2000).

Uric acid (MK) is the main product of the catabolism of purine nucleosides that are part of nucleic acids, macroergic compounds (ATP, ADP, AMP), some vitamins (Tits N.U. Clinical evaluation of laboratory tests. M., 1986). Hyperuricemia develops in all conditions in which the metabolism or degradation of nucleoproteins is enhanced (severe infections, tissue breakdown, pregnancy toxicosis, chronic kidney disease).

Putrescin, a biological amine belonging to the class of polyamines, accumulates in biological fluids and tissues during putrefactive processes, for example, with gangrene, lung abscesses, purulent peritonitis, is a toxic component of cavity media (Laboratory diagnosis of endogenous intoxication. In the book: Medical laboratory technologies. St. Petersburg, 2002, p.572).

Creatinine is the end product of nitrogen metabolism. An increase in its level is observed in case of impaired nitrogen-excreting function of the kidneys, with uremia, with liver failure.

Informative markers of endogenous intoxication are the presence in the blood serum of such amino acids as tryptophan, phenylalanine, histidine, isoleucine (Kuzin N.I., Kostyuchenok B.M. Wounds and wound infection. M., 1982; Dyachenko P.K. Pathogenesis and for the treatment of endotoxic shock // Vestn. Surgery. - 1980. - No. 11, - p. 3-9; Dorokhin K.M., Spas V.V. Pathophysiological aspects of endogenous intoxication syndrome // Anesthesiology and Intensive Care. - 1994. - No. 1, - p. 56-60; Malakhov M.Ya. Laboratory diagnosis of endogenous intoxication. In the book: Reference book. Medical laboratories new technologies.S.Peterburg. - 2002, - p. 571-599).

Various methods are currently used to diagnose endogenous intoxication: biochemical, biological testing, determination of toxicity of plasma serum by paramecium test, determination of mortality in the group of RES-blocked mice, determination of toxic effects on an isolated intestinal loop, determination of medium-weight molecules (MSM), Kishkun A.A. et al. The value of medium molecules in assessing the level of endogenous intoxication // Military Medical. Journal. - 1990. - No. 2, - p. 41-44. Obolensky S.V., Malakhova M.L. Laboratory diagnosis of intoxication in the practice of intensive care. S. Peter., 1999).

The analogue. A method for determining MSM. Determination of the fraction of medium-weight molecules in blood serum by protein precipitation with trichloroacetic acid (TCA) (Malakhova M.Ya., Solomennikov A.V., Belyakov N.A., Vladyka A.S. // Laboratory work. - 1987. - No. 3 , - p. 224-226).

The method is based on determining the optimal concentration of TCA, which would precipitate proteins, starting with a molecular mass of 10 kD and above, finding out the optimal wavelength at which it is advisable to conduct a study; determination of the possibility of research when freezing blood serum or storing it in the cold.

The express method for the determination of MSM consists in the fact that protein was precipitated in 1 ml of blood serum (SC) by adding 0.5 ml of a 10 or 15% TCA solution and, after centrifugation, spectrophotometry of the supernatant was carried out after dilution with distilled water in a ratio of 1: 9 over a range of lengths waves from 236 to 286 nm; Based on the obtained extinction values, spectrograms were built. In addition, the amount of protein was determined in the supernatant according to the Lowry method, based on the fact that about 85% of the substances in the MSM pool are of peptide nature.

The disadvantages of the method:

- violation of the nativeness of SC when 10 or 15% TCA solution is added to it;

- the use of a spectrometer device, which increases the cost of the method;

- difficulty in differentiating MSM, if in SC, for example, there are creatinine, uric acid, putrescine, amino acids.

Prototype. Biological express determination of toxic properties of SC using paramecium for endotoxemia (Pafomov G.A., Burdyga F.A., Shirinova M.N. Express method for determining the toxic properties of blood and lymph using paramecium for exo- and endotoxicosis // Soviet Medicine . - 1980. - No. 1, - p. 42-44).

The essence of the method is to change the timing of the death of Paramecium - the simplest ciliates under the influence of a toxic factor located in the UK.

For analysis, a pure line of Paramecium caudatum is used, which is grown in glass vessels in the infusion of hay, stem or banana peels in boiled water.

The method requires equipment:

- a microscope, glass slides, stopwatch, melanger, glass rod.

Study progress:

- Using a erythrocyte melanger, 0.01 ml of SC and an equal volume of suspension containing from 8 to 10 paramecia are applied to the glass, which is achieved by appropriate dilution of the culture medium in which the paramecium is cultivated.

- Both drops are thoroughly mixed, include a stopwatch.

- Determine the time of death of half the amount of paramecium (LD50) and the death of all cells (LD100).

- The sample is examined 3 times and average data is used.

As a biological control, the survival time of paramecia in the serum of healthy donors was determined, which on average was equal to LD50 (15-16 min) and LD100 (24-25 min).

The disadvantages of the method

1. The constant cultivation of paramecium.

2. Lack of information about differentiated indicators of toxicity of blood serum (its individual components).

3. The lack of the possibility of selective use of detoxification therapy.

Tasks:

1. Expanding the ability to diagnose endogenous intoxication.

2. To increase information content by highlighting selective markers of endotoxemia in SC.

3. Improve the accuracy and quality of diagnosis of endogenous toxicosis.

4. To increase the accuracy and adequacy of the provision of therapeutic care in the treatment process.

The essence of the method lies in the fact that for rapid diagnosis of endogenous intoxication, blood serum in drops, a volume of 0.01-0.02 ml, is applied to a slide, covered with a coverslip, dried at t = + 20-24 ° C for 1 -1.5 hours, kept in the open air for 1.5-2 hours, then microscopic in transmitted light, polarized and polarized with a quartz compensator, when studying the drug in transmitted light and in the presence of crystals in it: (and / or) - skeletal, stepwise, knotty fibrils, rectangular-branched aggregates of diag they test hyperglobulinemia, when studying the drug in polarized light and the presence of optically active crystals in it - radial beam spherulites, hypercholesterolemia is determined, needle-shaped - hyperuricemia, branching dendrites - hypercreatininemia, when studying the drug in polarized light with a quartz compensator and the presence of color in it (and / or) - plates, fan-shaped plates diagnose hyperputrescemia; ovoid grains - hyperphenylalaninemia; (and / or) - drusen, polyhedra and prisms - hyperhistidinemia; chain-oriented aggregation of grains - hypertryptophanemia; spherulitis with processes - hyperisoleucinemia; aggregates from grains - hyperbilirubinemia.

The method is as follows:

1. Produce a blood sampling from a vein - 3.0 ml, centrifuged to obtain serum.

2. Serum in the form of drops (5-6) with a volume of 0.01-0.02 ml each is applied to a glass slide, covered with a coverslip.

3. Dried in a thermostat at t = + 20-24 ° C for 1-1.5 hours.

4. Withstand outdoors 1.5-2 hours.

5. Under a microscope, in the transmitted, polarized and polarized with a quartz compensator light, the crystallization pattern is studied and, if there are crystals in the preparation in the transmitted light: (and / or) - skeletal, step, knotted fibrils, rectangular-branched aggregates, hyperglobulinemia is diagnosed, if hypercholesterolemia, needle-shaped - hyperuricemia, branching dendrites - hypercreatininemia, in the presence of polar in the preparation, in polarized light of optically active radial-ray spherulites Call light with a quartz compensator crystals variegated (and / or) - plates, fan-shaped plates diagnosed giperputrestsinemiyu; ovoid grains - hyperphenylalaninemia; (and / or) - drusen, polyhedra and prisms - hyperhistidinemia; chain-oriented aggregation of grains - hypertryptophanemia; spherulitis with processes - hyperisoleucinemia; aggregates from grains - hyperbilirubinemia.

When determining crystalline microtypes, the terminology used in mineralogy was used to define liquid crystalline microforms (A.N. Fedorov. The course of mineralogy and crystallography. St. Petersburg, 1901; Jale F.Kh. Polymer single crystals. L., 1968).

We previously prepared standard reference models containing the SC of a healthy person, enriched with various metabolites that appear during endogenous intoxication. For this purpose, SCs were placed in containers from quartz dishes and enriched in metabolites with a known concentration: globulins (α1-, α2-, β-, γ-fractions), creatinine, uric acid, putrescine, bilirubin, amino acids (phenylalanine, histidine, tryptophan , isoleucine).

Figure 1-15 shows the standard standards of crystallograms (SEC), developed by us models.

Hyperglobulinemia

SEC of the α1-globulin fraction shown in Fig. 1 contains skeletal crystals, the concentration of the fraction is 5.3%; SEC model α2-globulin fraction, figure 2 visible step crystals; fraction concentration - 10.9%; SEC models of the β-globulin fraction (16.8% concentration) are shown in FIG. 3, knotty fibrils are present; SEC models of the γ-globulin fraction are shown in Fig. 4, a concentration of 21.3% is seen in rectangular branched aggregates.

Hypercholesterolemia SEC is shown in figure 5, the concentration of cholesterol is 9.9 mmol / l, there is an optically active crystal - radial beam spherulite.

Hyperuricemia SEC is shown in Fig.6, there is a needle-shaped crystal of uric acid (MK), the concentration of which was 2.3 mmol / L.

Hypercreatininemia. SEC is shown in Fig. 7, there are branching optically active dendrites, the creatinine concentration is 3.2 mmol / L.

Hyperputrescemia. SEC is shown in Fig.8, 9; the concentration of putrescine, respectively, was 30 and 50 ng / ml, there are variegated fan-shaped plates. The studies were conducted in polarized light with a quartz compensator (QC).

Hyperaminoacidemia. SEC SK enriched with phenylalanine is shown in FIG. 10, concentration is 39 mg / l, ovoid grains are present, studies were performed in polarized light with QC. SEC SK enriched with histidine is shown in Figs. 11 and 12, the concentration was 30 and 45 mg / l, respectively, there are variegated polyhedra, prisms, druses. SEC SK enriched with tryptophan is shown in Fig. 13, concentration - 18 mg / l, colorful chain-oriented aggregations from grains are visible.

SEC SK enriched with isoleucine is shown in Fig. 14, the concentration is 50 mg / l, spherulite with processes is present.

Hyperbilirubinemia. SEC SK enriched with bilirubin is shown in Fig. 15, concentration is 45 μmol / L, motley aggregates from grains are visible.

The method was tested on 312 patients with endogenous intoxication syndrome.

Examples

Example 1, Fig. 16 a-z. B. I., medical history (IB) No. 192. Diagnosis (Ds): acute pancreatitis, pancreatic necrosis, diffuse purulent peritonitis. In Fig.16 a-c, crystallograms of SC of the 1st I. are shown. There are rectangular-branched aggregates (a), knotted fibrils (b), spherulites with processes (c), needle-shaped crystals (d), branching dendrites (e), plates and fan-shaped plates (g), polyhedra and prisms (h).

Technology: from a vein of the first I. blood sampling was carried out in an amount of 3 ml, which was centrifuged to obtain serum. Drops of SC (5) with a volume of 0.01 ml each were applied to slides and each covered with a coverslip. The preparation was dried in a thermostat at t = + 20 ° C for 1 hour, kept in the open air for 1.5 hours and studied under a microscope in transmitted, polarized light and in polarized light with CC. Found crystals represented by rectangular branched aggregates, nodular fibrils, spherulites with processes, needle-shaped crystals, branching dendrites, plates, polyhedra and prisms.

At the same time, the content of globulin protein fractions, isoleucine, MK, creatinine, putrescine, histidine was determined in the SC, which turned out to be elevated and, respectively, amounted to: γ-fraction - 24.3% (normal - 17.4%), β-fraction - 17.1 % (norm - 13.3%), isoleucine - 54 mg / l (norm 16 mg / l), MK - 2.9 mmol / l (norm 0.18 mmol / l), creatinine - 2.8 mmol / l (norm 0.044 mmol / l), putrescine - 38 ng / ml (norm 20 ng / ml), histidine - 39.0 mg / l (norm 12 mg / l). The alleged endogenous intoxication with globulins, isoleucine, creatinine, putrescine, histidine, uric acid was confirmed.

Example 2, FIG. 17 a-d. B-naya K., IS No. 238. Ds .: Acute endometritis, bilateral adnexitis, parametritis, sepsis. In Fig.17 a-d, serum KGs are shown, rectangular-branched aggregates (a), skeletal and step crystals (a, b), radial beam spherulites (c), ovoid grains (d), variegated chain-oriented aggregations from grains (d).

Technology: 3 ml of blood was taken from the vein of the patient K., which was centrifuged. Drops of SC (6) with a volume of 0.02 ml each were applied to slides and covered with coverslips, dried in a thermostat at t = + 22 ° C for 1.5 hours, kept in the open air for 1.5 hours and examined under a microscope in transmitted, polarized and polarized with CC light. The crystals were found: rectangular-branched aggregates, skeletal and step radial-ray spherulites, ovoid grains, variegated chain-oriented aggregations from grains. At the same time, the content of globulin protein fractions, cholesterol, phenylalanine, and tryptophan was determined in the SC, which turned out to be elevated and, respectively, amounted to: γ-fraction - 22.8% (norm 17.4%), α1-fraction - 5.5% (norm 3, 5%), α2 fraction - 11.3% (norm 7.8%), cholesterol - 11.8 mmol / l (norm 3.8 mmol / l), phenylalanine - 25 mg / l (norm 18 mg / l ), tryptophan 16 mg / l (normal 11 mg / l). Endogenous intoxication with globulins, cholesterol, phenylalanine, tryptophan was confirmed.

Example 3, Fig. 18 a-g. Bnoy N., IS No. 2113, Ds: Abscess of the right lung. Empyema of the pleura. Endotoxic shock. On Fig. 18 a-g are presented KG SC: knotted fibrils (a), rectangular-branched aggregates and step crystals (b), needle-shaped (c), radial-beam spherulites (c) with processes (d), plates (e), branching dendrites (g).

Technology: 3 ml of blood were taken from the vein of the patient N. and centrifuged. Drops of SC (5) each with a volume of 0.02 ml were applied to a glass slide, each covered with coverslips. The preparation was dried in a thermostat at t = + 23 ° С for 1 hour, kept in the open air for 2 hours and microscopied in transmitted, polarized light and polarized with CC. The crystals were found: nodular fibrils, rectangular branched aggregates, stepwise, needle-shaped, radial beam spherulites, spherulites with processes, plates, branching dendrites. At the same time, an increase in the content was determined in the SC: β-globulins - 22.9% (norm 13.3%), γ-globulins - 25% (norm 17.4%), α2-globulins - 13% (norm 7.8%) , MK - 4.3 mmol / l (norm 0.18 mmol / l), cholesterol - 13.4 mmol / l (norm 3.8 mmol / l), isoleucine - 30 mg / l (norm 16 mg / l) putrescine - 48 ng / ml (normal 20 ng / ml), creatinine - 2.9 mmol / l (normal 0.044 mmol / l). Endogenous intoxication with globulins, MK, cholesterol, isoleucine, putrescine, creatinine was confirmed.

Example 4, FIG. 19 a-k. F-boy F., IB No. 21, Ds: cirrhosis - liver cancer, ascites, liver failure, obstructive jaundice. On Fig a-k KG SC are presented: skeletal crystals (a), step (b), knotted fibrils (c), rectangular branched aggregates (d), variegated aggregates from grains (e), drusen (g), radially beam spherulites (h), ovoid grains (s), variegated chain-oriented aggregations from grains (k).

Technology: 3.0 ml of blood was taken from the vein of B.F., which is centrifuged. Drops of SC (6) each with a volume of 0.02 ml were applied to slides, each was covered with coverslips, dried in a thermostat at t = + 24 ° C for 1.5 hours and kept in the open air for 1.5 hours, microscopied in , polarized light and in polarized light with CC. The crystals were found: skeletal, stepwise, knotted fibrils, rectangular-branched aggregates, mottled-grain aggregates, Druze, radial-ray spherulites, ovoid grains, variegated chain-oriented aggregations from grains. At the same time, an increase in the content of globulins was determined in the SC: α1 fractions - 8.1% (norm 3.5%), α2 fractions - 17.5% (norm 7.8%), β fractions - 20.9% ( normal 13.3%), γ-fractions - 29% (normal 17.4%), bilirubin - 34 μmol / L (normal 8.2 μmol / L), histidine - 49 mg / L (normal 12 mg / L) cholesterol - 11.3 mmol / L (normal 3.8 mmol / L), phenylalanine - 36 mg / L (normal 18 mg / L), tryptophan - 23 mg / L (normal 11 mg / L). Endogenous intoxication with globulins, bilirubin, cholesterol, phenylalanine, tryptophan was confirmed.

Example 5, Fig. 20 a. B-Noi Sh., Information security No. 1116, Ds: traumatic shock, endotoxemia, compression syndrome, turnstile shock, acute renal hepatic failure. On Fig a-l presents the serum KG: skeletal crystals (a), step (b), knotted fibrils (c), branching dendrites (d), needle-shaped crystals (e), motley aggregates from grains (e), variegated polyhedra and prisms (g), variegated drusen (s), ovoid grains (s), chain-oriented aggregations from grains (k), spherulites with processes (l).

Technology: 3.0 ml of blood was taken from the vein of patient Sh., Which is centrifuged. Drops of SC (6), each with a volume of 0.01 ml, were applied to slides. Each was covered with coverslips, dried in a thermostat at t = + 23 ° C for 1.5 hours and kept in the open air for 2 hours, microscopic in transmitted, polarized light and in polarized light with a quartz compensator. The crystals were found: when examining in transmitted light - skeletal, stepwise, knotty fibrils; in polarized light - branching dendrites, needle-shaped; in polarized light with QC - motley crystals - aggregates from grains, polyhedra and prisms, druses, ovoid grains, chain-oriented aggregations from grains, spherulites with processes.

At the same time, an increase in the content was determined in the SC: α1-globulins - 8.2% (norm 3.5%), α2-globulins - 18.1% (norm 7.8%), β-globulins - 24.5% (norm 13 , 3%), uric acid - 3.8 mmol / L (normal 0.18 mmol / L), creatinine - 2.9 mmol / L (normal 0.044 mmol / L), histidine - 46 mg / L (normal 12 mg / l), tryptophan - 36 mg / l (norm 11 mg / l), phenylalanine - 36 mg / l (norm 18 mg / l), bilirubin - 38 μmol / l (norm 8.2 μmol / l), isoleucine - 29 mg / l (normal 16 mg / l). Endogenous intoxication with globulins, MK, cholesterol, bilirubin, creatinine, histidine, tryptophan, phenylalanine, isoleucine was confirmed.

The technical advantage of the method lies in the fact that the arsenal of diagnostic tests, which are markers of endogenous intoxication, is expanding. The proposed method creates the opportunity to reduce the cost of biochemical studies, is economically cheap. Up to 200 studies can be carried out during the day, depending on the current dynamics of the patient's condition and ongoing therapeutic measures.

The method can be widely used in medical institutions.

Claims (1)

A method for the rapid diagnosis of endogenous intoxication, including the study of blood serum and its microscopy, characterized in that drops of blood serum with a volume of 0.01-0.02 ml are applied to a glass slide, covered with a coverslip and dried in an thermostat for 1-1.5 hours at t = + 20-24 ° C, incubated in the open air for 1.5-2 hours, the drug is studied in transmitted, polarized light and in polarized light with a quartz compensator and when skeletal crystals (and / or) are detected in transmitted light, step, knotty fibrils, rectangular of complete aggregates - they diagnose hyperglobulinemia, when studying the drug in polarized light and identifying optically active crystals in it - radial beam spherulites - determine hypercholesterolemia, needle-shaped - hyperuricemia, branching dendrites - hypercreatininemia, when examining the drug in polarized light with quartz crystals of motley color (and / or) - plates, fan-shaped plates - diagnose hyperputrescemia; ovoid grains - hyperphenylalaninemia (and / or) - drusen, polyhedra and prisms - hyperhistidinemia; chain-oriented aggregation of grains - hypertryptophanemia; spherulitis with processes - hyperisoleucinemia; aggregates from grains - hyperbilirubinemia.

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