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Biomedical subjects

G Ellis

Publications and source records attributed to G Ellis.

At least 55 records · Page 3Linked to original sources

Serum 17 alpha-hydroxyprogesterone in infants and children as measured by a direct radioimmunoassay kit.

A direct 17 alpha-hydroxyprogesterone (17-OHP) radioimmunoassay kit was used for the assay of samples from 219 infants and children. The kit was used according to the manufacturer's protocol on unextracted serum or plasma and also on reconstituted material extracted from the serum with propanol-heptane. The extraction protocol recovers approximately 88% of 17-OHP. Patients were grouped as infants 3-90 days (96 subjects) or older children, adolescents and young adults 91 days-20 years (123 subjects). 17-OHP results by the direct and extraction protocols correlated but the slopes of the regression lines (0.43 and 0.63) differed in the two groups, indicating that only about 49% of the immunoreactive material measured by the kit in the infants was 17-OHP whereas the corresponding percentage was 72% in the older children. Despite this nonspecificity, the present antibody is much more specific for 17-OHP in the presence of neonatal plasma steroids than that used previously. Reference values were obtained for the two groups using the method with and without an extraction step. 17-OHP values on four untreated patients with CAH were clearly elevated at the time of diagnosis. It is recommended that when the kit is used with neonatal and infant samples, an extraction step should be incorporated to enhance specificity.

17-alpha-Hydroxyprogesterone↗

Primary hyperparathyroidism and coexisting nephrogenic diabetes insipidus: rapid postoperative correction.

Shortly after diagnosis of primary hyperparathyroidism, a patient had serum hyperosmolality, polyuria, isosthenuria, profound potassium depletion, and elevated plasma antidiuretic hormone levels, all consistent with nephrogenic diabetes insipidus. After parathyroidectomy, serum calcium and serum osmolality levels fell concurrently. Profound potassium deficits did not recur. We propose that (1) hypercalcemia produced a concentrating defect and polyuria; (2) renal tubular acidosis and polyuria combined to produce severe potassium depletion; (3) hypokalemia potentiated the nephrogenic diabetes insipidus caused by hypercalcemia; and (4) postoperative disappearance of the diabetes insipidus confirmed its reversible, purely metabolic causes.

Diabetes Insipidus↗

Use of the captopril test to assess renin responsiveness in children with hypertension and renal disease.

The captopril test was performed on 49 children of whom 36 were hypertensive, and the remainder were normotensive but were at risk for developing hypertension because of scarred kidneys secondary to vesico-ureteral reflux. Blood pressure (BP) was monitored in fasting supine patients throughout the duration of the test. Blood was taken for measurement of plasma renin activity (PRA); then captopril (0.7 mg/kg of body weight) was administered orally. A second blood sample was taken for PRA at 90 min postcaptopril. The mean (SEM) PRA at 90 min was 11.90 (4.01) ng/l/s [42.84 (14.44) ng/ml/h] in 7 patients with renovascular disease. In 4 patients with essential hypertension corresponding values were 0.88 (0.38) ng/l/s [3.17 (1.37) ng/ml/h]. Patients with other renal diseases showed variable values. Some individuals had PRA values as high as those of patients with renovascular disease, but the etiology of their hypertension was usually clinically evident. Our preliminary data would suggest that the captopril test may help differentiate between patients with essential hypertension and those with renovascular disease, or may help select patients that should be followed up by more definitive diagnostic procedures.

Captopril↗

Use of the captopril test to assess renin responsiveness in children with hypertension and renal disease.

The captopril test was performed in 49 children of whom 36 were hypertensive, and the remainder were normotensive but at risk for developing hypertension because of scarred kidneys secondary to vesicoureteral reflux. The blood pressure was monitored in fasting supine patients throughout the duration of the test. Blood was taken for measurement of plasma renin activity (PRA), then captopril (0.7 mg/kg body weight) was administered orally. A second blood sample was taken for PRA measurement 90 min after captopril administration. The mean PRA at 90 min was 11.90 +/- (SEM) 4.01 ng/l/s (42.84 +/- 14.44 ng/ml/h) in 7 patients with renovascular disease. In 4 patients with essential hypertension, the corresponding value was 0.88 +/- 0.38 ng/l/s (3.17 +/- 1.37 ng/ml/h). Patients with other renal diseases showed variable values. Some individuals had PRA values as high as those of patients with renovascular disease, but the etiology of their hypertension was usually clinically evident. Our preliminary data would suggest that the captopril test may help differentiate between patients with essential hypertension and those with renovascular disease or may help select patients that should be followed up by more definitive diagnostic procedures.

Adolescent↗

Sensitive time-resolved fluorescence immunoassay of somatotropin in serum.

We describe a new "sandwich"-type non-isotopic immunoassay for human somatotropin (GH, growth hormone) in serum. In the assay, GH is captured by a monoclonal antibody immobilized in a white microtiter well and simultaneously reacted with a second biotinylated monoclonal antibody. The degree of binding of biotinylated antibody, which increases with increasing amount of GH in the sample, is quantified by adding streptavidin labeled with the europium chelate of 4.7 - bis(chlorosulfophenyl) - 1.10 - phenanthroline - 2.9 - dicarboxylic acid. The fluorescent complex on the solid phase is then measured by excitation at 337.1 nm (nitrogen laser) and monitoring the emission at 615 nm in a gated fluorometer/analyzer. The proposed procedure has short incubation times (less than 4 h protocol), uses only 25 microL of serum per microtiter well, and gives precise and accurate results. The method was clinically evaluated with samples obtained from pediatric patients undergoing investigation for growth abnormalities and from a patient with acromegaly.

Acromegaly↗

Monoclonal antibodies for detection of occult carcinoma cells in bone marrow of breast cancer patients.

Metastases develop in 30% to 40% of patients with operable breast cancer. Investigators have reported on the detection of occult micrometastases in bone marrow using an antibody to epithelial membrane antigen (EMA) and have since reported prognostic significance for these antibody-detected cells. In this study, two anti-cytokeratin monoclonal antibodies (35 beta H11 and 34 beta E12) were used to examine bone marrow specimens from patients with breast cancer. The technique was first studied in a test system in which human or monkey bone marrow was seeded with MCF-7 cells, and was determined to be sensitive enough to detect fewer than one cancer cell in 10(4) hematopoietic cells. An immunoglucose oxidase method was used for patient specimen antibody localization and was found to be free of false-positive staining. Marrow specimens from 25 patients with breast cancer of various stages were examined. No correlation with disease stage was observed. We conclude that the technique is feasible, but prognostic import remains to be determined.

Antibodies, Monoclonal↗

A survey of observation units in the United States.

Observation units have been proposed as a tool in lowering over-all health care costs and increasing the quality of care in outpatient facilities. Emergency department (ED) use of these units has been evaluated at single facilities but never at a national level. A survey of 250 facilities across the United States was performed to gather information about the observation unit phenomenon. Of the 250 hospitals in the survey group, 27% had operational observation or holding units and another 16% planned units within 1 year. A statistically significant increase in the use of these units was noted in nonteaching facilities when compared with their teaching counterparts. A trend toward higher use of observation units in suburban/urban settings was noted when compared with rural locations, although the difference was not statistically significant. Of the units in existence, 93% were located within the ED, staffed by emergency physicians, and administrated by the ED director. Most are staffed by ED nurses and ancillary help. No hospital had both an ED unit and a non-ED unit, and many units functioned as both holding and observation areas. The units are perceived to be beneficial in patient care and in lowering health care casts, although objective documentation to validate these beliefs is lacking. Further prospective research is needed to evaluate these units scientifically before broad recommendations can be made.

Data Collection↗

Nonspecificity of a direct 17 alpha-hydroxyprogesterone radioimmunoassay kit when used with samples from neonates.

We analyzed 240 samples for 17 alpha-hydroxyprogesterone (17-OHP) with the direct-assay kit ("Coat-A-Count" method for serum samples) from Diagnostic Products Corp. (DPC). The specimens were from 50 patients with known or suspected congenital adrenal hyperplasia (CAH); 74 mostly hospitalized neonates and infants, ages three days to three months; and 116 other patients, ages six months to 23 years. Samples from the CAH group were also analyzed with our in-house assay. For 39 of the neonatal samples, the analysis with the DPC assay was repeated with re-solubilized material that had been extracted from the serum with organic solvents. Values for "17-OHP" measured with the DPC direct assay were high, not only in CAH patients, but also in many of the unaffected neonates and infants. The extraction properties of the cross-reacting immunoreactive material into various organic solvent systems were different from those of 17-OHP, and were more like those of steroid sulfates. Because of this significant cross-reactivity, we recommend that the DPC kit not be used for sera from children younger than six months of age, unless the method is modified to include an extraction step.

17-alpha-Hydroxyprogesterone↗

Amiodarone therapy effects on childhood thyroid function.

Thyroid function was systematically evaluated in 15 consecutive children (mean age 13.7 years, range 0.5 to 19.5 years) before and serially during treatment with amiodarone (Cordarone), a potent antiarrhythmic agent. Amiodarone is known to affect thyroid homeostasis by competitive inhibition of 5'-monodeiodinase, which converts L-thyroxine (T4) to triiodothyronine (T3) and reverse T3 (rT3) to 3,3'-diodothyronine (T2), and also by the direct effects of its high iodine content (37% by weight). Clinical and/or biochemical evidence of hypothyroidism occurred in three patients, two of whom required treatment with L-thyroxine. An additional patient had persistent hyperthyroxinemia but no clinical evidence of hyperthyroidism. Results from the patients who remained euthyroid showed characteristic alterations in serum thyroid function tests. These included significant increases in serum T4, rT3, basal thyroid-stimulating hormone and thyroid-stimulating hormone response to thyrotropin-releasing hormone testing. These changes were considered to be compensatory adjustments by the pituitary-thyroid axis to competitive inhibition of 5'-monodeiodinase by the amiodarone. Routine screening of thyroid function is needed to allow early detection of hypothyroidism when these compensations fail to occur.

Adolescent↗

Characterization of phosphohydrolase activity in bovine spleen extracts: identification of a bis(p-nitrophenyl)phosphate-hydrolyzing activity (phosphodiesterase IV) which also acts on adenosine triphosphate.

Several bovine spleen enzymes with acid pH optima, some of which hydrolyze bis(p-nitrophenyl)phosphate and therefore fit the definition of "phosphodiesterase IV," were partially separated by isoelectric focusing and ion-exchange techniques. The activities were characterized by zymogram analysis with the aid of p-nitrophenyl and 4-methylumbelliferyl phosphate and phosphonate substrates. A number of these enzymes meet the criteria for phosphodiesterase I or other phosphodiesterases. However, the predominant phosphodiesterase I hydrolyzes the bis(p-nitrophenyl)-and 4-methylumbelliferyl phosphates, p-nitrophenyl and 4-methylumbelliferyl phenylphosphonate, and ATP at the beta-gamma bond, but not p-nitrophenyl or 4-methylumbelliferyl 5'-thymidylate (the usual PDE I substrates). These properties, as well as the pH optimum, distinguish the activity from the previously described, alkaline pH optimum PDE I. A second phosphodiesterase hydrolyzes only the phenylphosphonates. Several other activities, less well described, are apparent on zymograms. None of the phosphodiesterases IV was also a phosphodiesterase II (no hydrolysis of 4-methylumbelliferyl 3'-thymidylate).

3',5'-Cyclic-AMP Phosphodiesterases↗

Serum dehydroepiandrosterone sulfate in a normal pediatric population.

Dehydroepiandrosterone sulfate (DHAS) was measured in serum from 274 children and adolescents aged 1 month to 18.7 years, and in 38 healthy adults. In the pediatric group, which comprised 131 males and 143 females, serum DHAS was markedly age-dependent. Values declined between 1 and 5 months after birth, but were generally less than 4 mumol/L. Between 6 months and 7 years DHAS was less than 0.5 mumol/L in boys and less than 1.0 mumol/L in girls. Above 8 years DHAS progressively increased in both sexes to less than 13 mumol/L in mid-late teenage males and less than 12 mumol/L in females of the same age, similar to the values observed in the adults. In children and adolescents over 10 years, there was considerable overlap in DHAS values between groups of children classified by pubertal stage, resulting from the dissociation between adrenal and gonadal development during normal puberty.

Adolescent↗

Myocardial ischaemia in asphyxia neonatorum. Electrocardiographic, enzymatic and histological correlations.

Serial electrocardiograms and creatine kinase (CK) isoenzyme activities were studied prospectively in 20 asphyxiated term newborn infants and 43 normal neonates. By adapting a previously described grading system for ischaemic changes, a degree of electrocardiographic ischaemia was defined which occurred almost solely in asphyxiated infants. Infants with this degree of abnormality had significantly higher mean CK-MB and MM activities than other asphyxiated infants at 0, 8 and 28 hours. Histological changes of peripartum myocardial necrosis were seen in 4 of the 5 infants on whom an autopsy was performed, and either electrocardiogram or CK-MB was abnormal in all four. It is concluded that myocardial injury in the newborn period is often associated with CK-MB release, but in view of the lack of cardiac-specificity of CK-MB in newborn infants, caution is urged in the interpretation of elevated isoenzyme activity in the neonate.

Asphyxia Neonatorum↗

An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c.

An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c is described. We use a 45-min incubation in acetate buffer (pH 5.5) to eliminate labile glycated hemoglobins. In this automated system conventional modules are used but it incorporates a solvent-switching valve to select either of two buffers, which differ in pH and NaCl concentration. The chromatographic column contains "polyCAT" (a weak cation-exchanger, polyaspartic acid linked to silica). Run time is 14 min per sample. The method is precise and results correlate well with those by other ion-exchange procedures.

Adolescent↗

A comparative study of 99mTc and 131I in thyroid scanning.

Thyroid scans performed with both 99mTc pertechnetate (99mTcO4) and (131I) were compared in 46 patients with palpable thyroid nodules to determine whether 131I scanning is any longer a necessary procedure. A discrepancy between the two types of scan existed in only three cases, in one of which the thyroid nodule showed uptake of 99mTcO4 but not of 131I. Subsequent surgery revealed a thyroid malignancy in this patient. In each of the other two discrepancies a nodule "cold" on 99mTcO4 scanning was apparently functioning on 131I scanning, and was found to be benign at surgery. As the convenience and lower radiation absorbed dose of 99mTcO4 patients compared with 131I make it a better scanning agent, it is recommended that 99mTcO4 scans of the thyroid be first nodules. If these nodules prove to be functioning equally with paranodular tissue, a 131I scan should also be performed to help exclude a possible thyroid malignancy.

Goiter↗