Reference values for blood findings in relatively fit elderly persons.

In a retirement community group of 73 relatively fit elderly white persons, a cross-sectional study of 53 different blood tests was conducted. The five test categories for blood values were hematology, chemistry, thyroid function, protein electrophoresis, and immunology. Fifteen percent of the blood findings were outside the range accepted as normal by the examining laboratories. Most of the subjects showed between 5 and 10 "abnormal" values within the five test categories. Since the findings were fairly predictable in view of the patho-anatomic changes that accompany aging, and since the manifestations of disease were at most subclinical, only minor alterations in individual management were needed. Subsequent appropriate clinical re-evaluation of these subjects during a six-month follow-up revealed no striking changes. It would appear that the ranges of "normal" reference values may need to be expanded. Although cross-sectional laboratory studies are useful, longitudinal studies seem essential if clinicians are to attain a more valid perspective.

Oestrogen--progestin therapy and the lipid balance of post-menopausal women.

The lipid and lipoprotein profiles of 20 post-menopausal women treated with cyclic conjugated oestrogens (0.625 or 1.25 mg) and medroxyprogesterone acetate (10 mg for 7 days) were compared to those of 18 untreated women of similar age and menopausal status. No statistically significant between-group differences were observed during the 18-mth period for cholesterol, triglycerides or lipoprotein distribution. After 12 mth, a significant shift in lipoprotein distribution manifested in the treated and untreated groups. The proportion of high-density lipoproteins significantly increased and that of the low-density lipoproteins significantly decreased. Although the shift was more pronounced in the treated group, there was no significant difference between the treated and untreated groups. These results indicated that such relatively nonandrogenic progestins as medroxyprogesterone acetate, have no adverse effects on the lipid milieu of post-menopausal women when used with long-term oestrogen therapy.

Comparison of serum bilirubin levels in humans and two monogastric animal species after a single administration of sulfisoxazole.

Administration of sulfonamides during periods of hepatobiliary failure or hepatic immaturity increases the toxic potential of unconjugated or indirect bilirubin. A small but statistically significant increase of indirect, or unconjugated bilirubin was noted in dogs after oral administration of sulfisoxazole (100 mg/kg). A similar increase was not observed in swine after oral or intravenous administration of sulfisoxazole (100 mg/kg) or in humans (approximately 28 mg/kg) after oral administration or in dogs (100 mg/kg) after intravenous administration. Total and conjugated bilirubin showed small but statistically significant increases and were significantly correlated in dogs after oral and intravenous administration of sulfisoxazole (100 mg/kg) and in swine after oral administration of sulfisoxazole (100 mg/kg). There was a significant negative correlation between conjugated and indirect bilirubin, while total bilirubin increased in dogs after oral and intravenous administration of sulfisoxazole. These data illustrate a difference in species and administration route when attempting to assess the potential toxicity of bilirubin.

Blood and ruminal fluid profiles in carbohydrate-foundered cattle.

The relationships of acetylhistamine and histamine to the clinical signs of carbohydrate-induced acidosis were investigated in beef steers. Blood pH and plasma L-lactic acid decreased and serum sodium, serum potassium, ruminal fluid L-lactic acid, ruminal fluid histamine, and ruminal fluid and blood acetylhistamine increased in carbohydrate-engorged steers as compared with the changes in the steers while feeding on pasture (forage-fed steers). Twelve to 14 hours after the steers had become engorged, clinical signs of laminitis ("feedlot founder") were observed in three of six steers. These signs appeared 4 to 6 hours after blood acetylhistamine attained maximal concentration (2.9997 +/- 1.7054 microgram of histamine base/ml of blood) and blood pH decreased to 7.260 +/- 0.026 at 8 hours after engorgement. Blood histamine value reached 0.1298 +/- 0.1095 microgram of histamine base/ml 4 hours after engorgement (8 to 10 hours before the appearance of clinical illness), but had reached maximal concentration 32 hours after engorgement (0.3300 +/- 0.028 microgram of histamine base/ml of blood).

Establishing a multivariate clinical laboratory data base.

A regional or hospital-based "reference" value study is well within the range of every clinical laboratory. A program is described that samples one to two "health" subjects each working day under tightly controlled conditions. Sixty-seven variables are tested simultaneously to provide univariate age and sex ranges, and variance/covariance matrices from which associated correlation coefficients are obtained. This ongoing "reference" value program offers essential information for both univariate and multivariate interpretations along with validation and quality control for certain methods within the clinical laboratory.

Evaluation of a rapid immunoassay for monitoring serum pentobarbital concentrations.

A modification of the EMIT-Tox qualitative serum barbiturate assay (Syva Company, Palo Alto, CA) was evaluated for measuring pentobarbital concentrations. Pentobarbital calibrator solutions were substituted for the secobarbital calibrators provided with the assay kit, and control solutions of pentobarbital were used to determine the modified assay's precision and accuracy. Specificity for pentobarbital with respect to other barbiturates and assay interference from other drugs were evaluated in vitro. Serum samples obtained from 49 patients receiving intravenous pentobarbital sodium to treat intracranial hypertension were assayed by gas-liquid chromatography (GLC) and by the modified EMIT procedure. Samples from patients who were receiving both phenobarbital and pentobarbital (9 of 49) were assayed for both drugs, interference curves were plotted, and the corrected pentobarbital concentrations were compared with GLC values. The modified assay method provided an accurate measurement of serum pentobarbital concentrations of 1-30 micrograms/ml. Significant cross-reactivity with the pentobarbital assay was present for secobarbital, butabarbital, allobarbital, and phenobarbital. Dexamethasone, dopamine, phenytoin, cimetidine, lidocaine, diazepam, morphine, and several other drugs at concentrations of 1000 micrograms/ml did not interfere with the assay. There was a strong correlation between the GLC reference method and the modified EMIT assay (r = 0.96). Clinically important cross-reactivity with phenobarbital was found; the corrected pentobarbital concentrations for patients who had received phenobarbital strongly correlated with GLC results (r = 0.98). The modified assay appears to be sufficiently reliable for determination of pentobarbital serum concentrations.

Lipids and lipoproteins in women after oophorectomy and the response to oestrogen therapy.

The short-term effects of different types and doses of oestrogen on serum lipids and lipoproteins were studied in 35 oophorectomized women. After 3 months treatment, serum cholesterol levels were unaffected by 1 and 2 mg of micronized 17 beta-oestradiol or 0.625 and 1.25 mg of conjugated equine oestrogens. Triglyceride levels were significantly elevated after treatment with 1.25 mg of conjugated oestrogens. A trend towards a higher relative proportion of high-density lipoproteins and a lower relative proportion of low-density lipoproteins was observed for all four oestrogen regimens, however, statistical significance was not achieved. The proportion of very-low-density lipoprotein was unaffected by oestrogen treatment. The age of the oophorectomized women was found to have no effect on either the direction or magnitude of the lipid or lipoprotein responses to oestrogen. Using FSH depression as an index, 1.25 mg of conjugated oestrogens was found to be the most potent of the four oestrogen regimens tested. Therefore, with respect to lipid balance, little additional clinical benefit is achieved by using a more potent regimen and the risk of adverse side effects may be increased.

Double-antibody fluorescence immunoassay of tobramycin.

This heterogeneous assay for tobramycin involves fluorescein-labeled tobramycin, which competes with native unlabeled tobramycin for anti-tobramycin binding sites. Bound and free labeled antigen are separated by precipitation with a second antibody. Fluorescence intensity of the resuspended precipitate is inversely proportional to native tobramycin concentration. Background interference was consistently about 10% of the total fluorescence precipitated. Assay sensitivity was sufficient to detect nanogram quantities of tobramycin per assay tube. Correlation coefficients (r) were 0.96 and 0.98 for comparisons of this assay with a microbiological assay and a radioimmunoassay, respectively. Mean analytical recovery was 101% and the CV was less than 10% throughout the therapeutic range.