A rapid dietary screening device for clinics.

A rapid dietary screening device was developed for use in clinics and tested for validity, reliability, and acceptability. Validity was tested using dietary information from 29 8-day weighed food diaries. For each diary, a score was derived by calculating a mean Nutrient Adequacy Ratio (NAR) for nine nutrients. Dietary information from each diary was also entered on the Dietary Intake Form (DIF). The relationship of the mean NAR and DIF scores had a positive correlation of 0.83. Reliability was determined by testing undergraduate students in a non-nutrition course twice, two weeks apart. Forty repeated paired food group and total dietary scores revealed positive correlations, with r = 0.81 for total dietary score, 0.91 for dairy products, 0.78 for protein, 0.80 for fruits and vegetables, and 0.88 for bread. Acceptability of DIF was measured by the time it took to fill out and evaluate it, as well as by the percentage of incomplete DIFs. The subjects included 135 women aged 12 to 50 years from three Northeastern Oklahoma Planned Parenthood clinics. The mean time to fill out and evaluate the DIF was 4 to 7 minutes. Seventy-nine percent of the individuals tested were able to complete the DIF. Dietary patterns could not be predicted in this population by age, income level, education level, race, or clinic site. The DIF provides a rapid, valid, reliable, and acceptable method of identifying the individual with a poor diet. Because it does not require the expertise of a nutritionist either for its completion or for its evaluation, this device permits the dietitian to allocate her/his time more effectively under time and cost limitations.

Thymidine kinase: a tumor marker with prognostic value for non-Hodgkin's lymphoma and a broad range of potential clinical applications.

Thymidine kinase (TK) is a cellular enzyme which is involved in a "salvage pathway" of DNA synthesis. It is activated in the G1/S phase of the cell cycle, and its activity has been shown to correlate with the proliferative activity of tumor cells. Additionally, certain viruses are able to induce cellular TK production and activity. Clinical studies have reported elevated serum TK levels in a variety of neoplasias. The majority of these studies concerned hematologic malignancies. TK seems to be a useful marker in non-Hodgkin's lymphoma, where it correlates with clinical staging and provides significant prognostic information on (progression-free) survival. Preliminary results in acute myeloid leukemia indicate that pretreatment serum TK values may predict the response to the first induction chemotherapy. Moreover, serum TK appears to have some clinical value in such solid tumors as prostate cancer, breast cancer, and small-cell lung cancer, whereas it is not a reliable marker of non-small-cell lung cancer and brain tumors.

Activity of serum thymidine kinase in non-Hodgkin lymphoma: relationship to other prognostic factors.

The value of serum deoxythymidine kinase (TK) for the staging and evaluation of disease activity of non-Hodgkin lymphoma (NHL) as compared with serum beta 2-microglobulin, serum lactate dehydrogenase, blood sedimentation rate, blood hemoglobin, white blood cell count, lymphocyte count and platelet count was investigated in 101 patients. In addition, the performance status was determined by the Karnofsky index. Patients with chronic lymphocytic leukemia (CLL; n = 43) and immunocytoma (IC; n = 19) were staged according to the Binet classification, and the other low (n = 28) and high grade NHL (n = 8) according to the Ann Arbor classification. The analysis of all CLL and IC patients revealed that TK values correlated better with Binet stages (p = 0.01; n = 58) than blood sedimentation rate (p = 0.05, n = 12), lactate dehydrogenase (p = 0.08; n = 50), beta 2-microglobulin (p = 0.29; n = 28), lymphocyte count (p = 0.70; n = 57), white blood cell count (p = 0.69, n = 59) and the Karnofsky index (p = 0.16, n = 50). Mean TK levels of these patients were for Binet stage A 6.2 +/- 0.8 U/l (mean +/- S.E.M., range 2.3-18.0), stage B 13.3 +/- 6.5 U/l (3.8-38.8) and stage C 19.6 +/- 4.4 U/l (1.9-79.0), and for 22 healthy controls 3.8 +/- 0.2 U/l (2.2-6.0). Patients with multiple courses of chemotherapy (n = 32) previous to the study had significantly (p = 0.01) higher TK levels (16.4 +/- 3.7 U/l; 2.3-79.0) than those with only up to one course (n = 66; TK: 8.6 +/- 1.4 U/l; 1.5-66.3). The follow-up of 16 patients with low grade NHL showed that serum TK levels paralleled well the clinical response. The results indicate that TK might be a worthful parameter to estimate progression and response to therapy of NHL.

Investigations on the metabolic pathways of cyclosporine: II. Elucidation of the metabolic pathways in vitro by human liver microsomes.

1. Cyclosporine and its metabolites, isolated from human bile and identified by FAB mass spectrometry and 1H-n.m.r. spectroscopy, were metabolized by human liver microsomes for the identification of new cyclosporine metabolites. From these data a metabolic pathway for cyclosporine, which includes these new cyclosporine metabolites, has been proposed. The new metabolites were isolated by semi-preparative h.p.l.c. and their chemical structures were elucidated by FAB mass spectrometry. These isolated metabolites were further metabolized and the products identified by FAB mass spectrometry. 2. Fourteen metabolites, whose structure has not yet been elucidated, were isolated after metabolism of structurally identified cyclosporine metabolites, and chemical structures for five of these metabolites were proposed. 3. The structures of the new cyclosporine metabolites were: (i) a N-demethylated, carboxylated derivative (AM1A4N), (ii) a di-hydroxylated, N-demethylated derivative (AM14N9), (iii) a hydroxylated and carboxylated derivative (AM1A9), (iv) a di-hydroxylated, cyclized and N-demethylated derivative (AM1c4N9) and (v) a cyclized and carboxylated (AM1cA) derivative. 4. A proposed cyclosporine metabolic pathway comprises a total of 29 metabolites. It consists of four main branches originating from metabolites AM1, AM1c, AM9 and AM4N.

Investigations on the metabolic pathways of cyclosporine: I. Excretion of cyclosporine and its metabolites in human bile--isolation of 12 new cyclosporine metabolites.

1. Cyclosporine metabolites of known and unknown structures were isolated, by semi-preparative h.p.l.c., from human bile from the T-tube of liver-grafted patients, who received cyclosporine treatment. Their structures were elucidated by FAB mass spectrometry and 1H-n.m.r. spectroscopy. 2. Twelve of the cyclosporine metabolites, with known chemical structures, were isolated and identified using authentic standard material. 3. Four isolated fractions contained tri-hydroxylated metabolites; two fractions contained di-hydroxylated, demethylated metabolites; one fraction contained a tri-hydroxylated, demethylated metabolite; and one fraction a mono-hydroxylated, demethylated metabolite. The exact metabolism sites were partially defined. 4. Two carboxylated cyclosporine metabolites, of which one was hydroxylated in an unknown position, were isolated. 5. One new metabolite proved to be a glucuronylated phase II metabolite. Deglucuronylation of this metabolite by beta-glururonidase yielded metabolite AM1c. The proposed structure was AM1c-Glc; is a proposed extension of the Hawk's Cay nomenclature of the cyclosporine metabolites for glucuronylated metabolites. 6. One of the unknown metabolites was hydroxylated in two positions of amino acid 1. The proposed nomenclature was 'AM11d', where '1d' indicates hydroxylation at the delta C of amino acid 1. 7. A metabolite with an aldehyde functional group at amino acid 1, which had two isomeric forms, was isolated. I.r.-spectroscopy indicated that isomerism may be caused by conjugation of the aldehyde group with the double bond between C6 and C7 of amino acid 1.

Urinary excretion of ciclosporin and 17 of its metabolites in renal allograft recipients.

Renal elimination of the immunosuppressant ciclosporin is virtually unknown. Therefore, in 17 renal allograft recipients under steady-state conditions we studied the urinary excretion of ciclosporin and 17 of its metabolites in blood and 24-hour urine. Patients with liver dysfunction or treated with drugs potentially influencing the metabolism and elimination of ciclosporin were excluded from the study. Ciclosporin and its metabolites were measured by HPLC. Metabolite but not ciclosporin excretion was strongly correlated with creatinine clearance. Metabolites 18 and 26 (beta, epsilon-cyclic metabolite) were rarely found in blood but were excreted in considerable amounts in urine. Approximately 3% of the administered dose of ciclosporin per day undergoes renal elimination in unchanged form or as metabolites investigated. The data suggest glomerular filtration of ciclosporin metabolites, a difference in the rate of elimination between ciclosporin and the metabolites and some kind of metabolism or active transport mechanism for metabolites in the kidney.

Ciclosporin metabolite pattern in blood and urine of kidney graft patients in relation to liver function.

Ciclosporin, an immunosuppressant, is metabolized by the liver cytochrome P450 system. Changes in the pattern of its metabolites in blood and urine in patients with disturbed liver function have been studied. Forty seven kidney graft patients receiving 2.9 mg/kg/d ciclosporin b.i.d., and no additional medication that would interfere with ciclosporin metabolism, were allocated to three groups according to liver function: I with normal liver function (n = 19), II with elevated liver enzyme activity or bilirubin concentration in serum (n = 20), and III with cholestasis (n = 8). Ciclosporin and 17 metabolites were determined in blood and 24 h-urine. In blood the trough concentrations of metabolites M19 and M1A were significantly higher in group III than in groups I and II. The total quantity of metabolites excreted in 24 h-urine was significantly different for H230, M4N69 and M1A (group III greater than I = II). Renal excretion of the daily dose of ciclosporin in patients in group I was 2.7%, group II 3% and group III 5.7%. In group III compared to group I the ciclosporin metabolite pattern was shifted to a relatively higher concentration of M19 in blood and of H 230, M19 and M1A in urine. Since high ciclosporin metabolite concentrations appear to be associated with nephrotoxicity, the metabolite pattern in patients with impaired liver function should be monitored.

Assignment of weight-based antibody units to a human antipneumococcal standard reference serum, lot 89-S.

A human reference serum pool, lot 89-S, has been developed for use in quantitating concentrations of antibody to Streptococcus pneumoniae. Weight-based units have been assigned to antibodies to 11 pneumococcal polysaccharide (PnPs) serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) by using enzyme-linked immunosorbent assay methodology and a human standard reference serum, USNRP IS 1644. The experimentally derived assignments for anti-PnPs antibodies of the immunoglobulin G (IgG), IgM, and IgA isotypes in lot 89-S correlate well to the separately determined immunoglobulin assignment. These assignments for this antipneumococcal standard serum were used to quantitate IgG, IgM, and IgA isotype levels and the total immunoglobulin level in pediatric samples from a pneumococcal conjugate vaccine trial. The data indicate that these assignments may be used to assess levels of antibody to PnPs serotypes in human serum.