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Biomedical subjects

J W Ryan

Publications and source records attributed to J W Ryan.

At least 55 records · Page 3Linked to original sources

Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys.

We have evaluated the biodistribution of human low-density lipoprotein (LDL) radiolabeled with 99mTc or with 123I-tyramine cellobiose in rabbits and in rhesus monkeys. Biodistribution was assessed after intravenous injection of radiolabeled LDL by quantitative analysis of scintigrams, counting of excreta, and counting of tissues at necropsy. Both rabbits and monkeys showed lower renal uptake (123I:99mTc approximately 1:3, as regional percent injected activity corrected for physical decay) and excretion (1:2 to 1:4), but higher hepatic (1.5:1 to 2:1) and cardiac (1.7:1 to 4:1) uptake of 123I than of 99mTc. Adrenals were visualized in normolipemic animals with 123I-tyramine cellobiose-LDL but not with 99mTc-LDL. Hyperlipemic animals showed increased cardiac (up to six-fold) and decreased hepatic activity (by 50%-60%) of both radionuclides. We conclude that 123I-tyramine cellobiose-LDL is better suited than 99mTc-LDL for dynamic studies of LDL metabolism in vivo.

Animals↗

Detection and assessment of severity of tricuspid regurgitation using first-pass radionuclide angiography and comparison with pulsed Doppler echocardiography.

Noninvasive detection and semiquantitative assessment of tricuspid regurgitation (TR) were performed using first-pass radionuclide angiography (RNA), by sampling a region of interest over the right atrium for any tracer entering the right atrium during right ventricular systole. The relative amount of tracer entering the right atrium was quantitated and the results were compared with semiquantitative Doppler echocardiographic grading of TR severity. Using the right ventricular time-activity curve to define end-diastolic and end-systolic frames, the right atrial counts for the 2 or 3 cardiac cycles after the peak right ventricular counts were summed. The right atrial "injection fraction" was calculated using the following formula: [(end-systolic counts - end-diastolic counts)/(end-diastolic counts)] X 100%. The right atrial injection fraction was examined in 51 patients who had good quality RNA and Doppler studies. Of 27 patients with no evidence of TR by Doppler, 26 had a negative right atrial injection fraction. All 24 patients with a positive Doppler for TR had a positive right atrial injection fraction. Comparison of right atrial injection fraction grade ranges with semiquantitative grades of TR severity on Doppler revealed identical grades in 21 of the 24, with a single grade difference in the remaining 3 patients. Thus, right atrial time-activity curve quantitation during routine first-pass RNA allows detection and grading of the severity of TR, with results very similar to pulsed Doppler echocardiography. This simple procedure is easily appended to the evaluation of ventricular performance with first-pass RNA.

Adolescent↗

The process of rater training for observational instruments: implications for interrater reliability.

Although the process of rater training is important for establishing interrater reliability of observational instruments, there is little information available in current literature to guide the researcher. In this article, principles and procedures that can be used when rater performance is a critical element of reliability assessment are described. Three phases of the process of rater training are presented: (a) training raters to use the instrument; (b) evaluating rater performance at the end of training; and (c) determining the extent to which rater training is maintained during a reliability study. An example is presented to illustrate how these phases were incorporated in a study to examine the reliability of a measure of patient intensity called the Patient Intensity for Nursing Index (PINI).

Employee Performance Appraisal↗

Inhibition of endothelial-bound angiotensin converting enzyme, in vivo.

1. We determined apparent Ki constants of two inhibitors, captopril and CL242,817, for pulmonary endothelial-bound angiotensin converting enzyme (ACE) in anaesthetized rabbits. [3H]-benzoyl-Phe-Ala-Pro was used as the substrate. The apparent kinetic parameters Km and Amax (product of Vmax and microvascular plasma volume) were measured, as was the ratio (Amax/Km) (measured under first order reaction conditions) before and 30s after the i.v. administration of captopril 10 nmol kg-1 or CL242,817, 35 nmol kg-1. 2. Under mixed order reaction conditions, ([S] greater than or equal to Km), apparent Km values increased from 12.2 +/- 1.9 microM to 32.9 +/- 3.3 microM (P less than 0.05) in the captopril-treated rabbits and from 9.3 +/- 2.3 microM to 45.8 +/- 9.8 microM (P less than 0.05) in the CL242,817-treated rabbits, indicative of competitive inhibition. However, apparent Amax values decreased from 10.3 +/- 2.1 to 4.5 +/- 0.8 mumol min-1 (P less than 0.05) and 8.9 +/- 1.7 to 4.8 +/- 0.5 mumol min-1 (P less than 0.05), respectively. 3. Under first order reaction conditions ([S] much less than Km), the Amax/Km ratio decreased from 763 +/- 100 to 125 +/- 38 ml min-1 (P less than 0.05) and 1009 +/- 149 to 126 +/- 44 ml min-1 (P less than 0.05) in the captopril- and CL242,817-treated groups respectively. 4. When the single pass transpulmonary binding of 80pmol [3H]-RAC-X-65 (an ACE inhibitor) was measured in additional rabbits, a significant (P < 0.05) decrease in RAC-X-65 binding was observed 30s after captopril (80% decrease) or CL242,817 (85% decrease), a result expected for a loss of catalytically active enzyme mass due to tightly bound captopril or CL242,817. 5. These results indicate that, in vivo, both captopril and CL242,817 are competitive, tight binding inhibitors of lung ACE. Furthermore, they suggest means for evaluating the interaction of other potential ACE inhibitors with the pulmonary endothelial membrane-bound enzyme, in vivo, possibly in phase I clinical trials.

5'-Nucleotidase↗

Efficacy of computed tomography of the thorax and upper abdomen and whole-body gallium scintigraphy for staging of lung cancer.

To assess the efficacy of performing both computed tomography (CT) of the thorax and upper abdomen and whole-body gallium scintigraphy for staging lung cancer, the results of each test were compared with those obtained by chest radiography and clinical examination in 100 patients. Clinical efficacy was defined in terms of accuracy in staging the tumor based either on surgery, biopsy, or clinical and radiologic follow-up. The CT provided significantly superior accuracy in 27 patients and minor additional staging information in 17 patients compared with the gallium scan. Whole-body gallium scintigraphy provided important additional information in nine patients and minor additional information in a further eight. The diagnostic yield of CT and gallium scanning was considered equivalent in 39 cases. Of the nine cases in which gallium was significantly superior to CT, clinical findings which suggested the presence of metastases had been noted before the scan in four cases. The authors' results confirm the utility of CT for staging lung cancer and indicate that the additional yield from gallium scintigraphy is relatively low provided a thorough history and physical examination have been performed.

Adult↗

Localization of angiotensin-converting enzyme in the trout gill.

Angiotensin-converting enzyme (ACE) was localized in perfused trout gills by measuring gill extraction of two radiolabeled ACE inhibitors, 125I-351A (an iodinated derivative of lisinopril) and 3H-RAC-X-65, and by autoradiography of gills perfused with 125I-351A. A 125I-351A pulse was preferentially extracted by the arterio-arterial (AA) pathway (61.7% +/- 1.8% extraction; mean +/- SE, N = 4); the arteriovenous (AV) pathway extracted an additional 10%. Extraction by either pathway was reduced by simultaneous perfusion with 10(-5) M unlabeled lisinopril. AA extraction of RAC-X-65 during continuous perfusion was maximal (75% +/- 5%, N = 6) during the first few minutes of perfusion and decreased steadily to 38% +/- 9% by 20 min and to less than 10% by 40 min. AV extraction of RAC-X-65 was negligible. Autoradiography of gills continuously perfused with 125I-351A showed that the radiolabel was concentrated in the respiratory lamellae. The highest grain density was associated with the pillar cells nearest the medial (inner) lamellar margin. Afferent filamental arteries and afferent lamellar arterioles were labeled to a lesser extent. Relatively little label was found on the efferent lamellar arterioles or efferent filamental arteries. 125I-351A binding was not evident in AV vessels. These findings support the hypothesis that the gill is an important site for formation of plasma angiotensin II and they suggest that enzymes associated with mammalian endothelial cells are also common to gill pillar cells.

Animals↗

Planar positron imaging of rubidium-82 for myocardial infarction: a comparison with thallium-201 and regional wall motion.

Rubidium-82 (Rb-82) is a generator-produced, short half-life (76 seconds) positron emitting potassium analog. Using a mobile gamma camera equipped with a rotating tungsten collimator and high-energy shielding, we examined the use of Rb-82 in the coronary care unit and clinical laboratory for detection of perfusion defects due to myocardial infarction. We studied 31 subjects, 10 patients with acute myocardial infarction, 12 with remote myocardial infarction, and nine controls. Rb-82 images were compared with Tl-201 and regional wall motion for detection of infarct-related arteries. Of the 22 patients with myocardial infarction, 16 were identified with Rb-82 and Tl-201. In nine control subjects, eight were normal with each method. Correlation between Rb-82 and Tl-201 defect scores was excellent. Sensitivity and specificity for infarct-related arteries were similar for Rb-82, Tl-201, and wall motion imaging. Thus planar Rb-82 imaging can detect MI reliably in the coronary care unit and in the clinical laboratory.

Coronary Care Units↗

Peptidase enzymes of the pulmonary vascular surface.

No fewer than five peptidase enzymes are disposed on the pulmonary vascular surface and are capable of reacting with peptides (including peptide hormones and pro-hormones) within the intravascular space. The review that follows describes these enzymes and their actions and suggests how the enzymes may be assayed in vivo to improve understanding of pulmonary microvascular functions as well as aspects of endocrinology.

Amino Acid Sequence↗

Measuring patient intensity. A reliability study.

The purpose of this study was to determine the interrater reliability for each of 12 dimensions of a measure of Patient Intensity for Nursing (PINI). Three hospitals in two states participated in this project with 121 Registered Nurses prepared in the use of the PINI. The interrater reliability was determined by day shift nurses rating their patients late in the shift and evening shift nurses rating the same patients early in their shift. Paired ratings of 657 patients were included in this analysis, and the reliability was substantial (kappa = greater than .60) for 10 of the 12 dimensions across hospitals. These findings provided the foundation for revision of the instrument, which is currently undergoing additional testing.

Activities of Daily Living↗

Difficulties of parathyroidectomy after previous thyroidectomy.

Although the risks of reoperative thyroidectomy and parathyroidectomy have been well studied, the problems associated with parathyroidectomy after prior thyroidectomy have not been emphasized. Among a group of 282 patients who were treated for primary hyperparathyroidism in recent years at the University of Chicago Medical Center, 14 (4.8%) had undergone one or more previous thyroidectomies, and 6 others (2.1%) had undergone thyroid ablation with radioactive iodine as therapy for Graves' disease. Numerous difficulties were encountered during surgery in the postthyroidectomy group of patients as a result of scarring and fibrosis, prior recurrent laryngeal nerve injuries in 13%, the inability to known with certainty how many viable, normal parathyroid glands remained after previous operations, and the need for additional thyroid resection, mostly for associated malignant lesions. Preoperative vocal cord assessment, evaluation of prior operative and pathology reports, and localization studies with thallium-technetium scanning and ultrasonographic techniques were especially helpful. A "lateral approach" was used frequently during surgery. Each of these 14 patients was cured of the hyperparathyroidism. The postthyroid ablation group presented fewer intraoperative challenges, although in some patients the thyroid gland was virtually absent, which obscured the normal landmarks of the surgical field. Five of these six patients were cured of hyperparathyroidism. Parathyroidectomy after thyroidectomy presents many operative challenges to the surgeon and should be approached with the same care and concern that one reserves for a reoperative parathyroid operation.

Adult↗

Combined bone marrow and gallium imaging. Differentiation of osteomyelitis and infarction in sickle hemoglobinopathy.

The clinical records and scintigrams of patients with sickle hemoglobinopathy who underwent combined Tc-99m bone marrow imaging and Ga-67 imaging to differentiate osteomyelitis from bony infarction were reviewed. Of 18 paired examinations in 15 patients, osteomyelitis was diagnosed correctly in six cases; in all six, gallium uptake at the symptomatic site was incongruently increased relative to the bone marrow activity. Of the 12 episodes of infarction, 11 showed congruent activity on both Tc-99m and Ga-67 images. The remaining study was interpreted incorrectly as osteomyelitis due to incongruent Tc-99m and Ga-67 uptake. The use of sequential Tc-99m bone marrow and Ga-67 imaging is an effective means of distinguishing osteomyelitis from bony infarction in patients with sickle hemoglobinopathy.

Adolescent↗

Angiotensin-converting enzyme in bovine, feline, and human ocular tissues.

Angiotensin-converting enzyme was shown to be present in retinal vessels and neural retina of feline, bovine, and human eyes. It was also demonstrated in the other ocular tissues of feline eyes, in especially high concentration in the highly vascular uveal layer. Its role in the physiology of ocular blood flow and neurophysiology is uncertain, especially in the retina where circulating angiotensin and bradykinin are confined to the intravascular space by the blood-retina barrier, and sufficient data are not available to describe these peptides as transmitters or modulator molecules in the retina.

Angiotensin-Converting Enzyme Inhibitors↗

In-line measurement of pulmonary metabolic function in the anesthetized rabbit.

Quantitative assessment of lung metabolic function is thought to provide biochemical information reflecting integrity of the pulmonary microcirculation. Although multiple indicator-dilution techniques are useful in such pharmacokinetic studies, the need for fractionation and subsequent processing of blood samples greatly prolongs data generation. Accordingly, we designed and tested an in-line system which rapidly can quantify single-pass disposition of photon-emitting substances in the pulmonary circulation of intact animals. The nuclear detection system consisted of a phoswich scintillation probe optically coupled to a photomultiplier tube. Pulses were discriminated for height and shape and counts recorded in a counter-timer, the output of which was interfaced with a personal computer. A mixture of an intravascular reference substance (99mTc-sulfur colloid) and an inhibitor of angiotensin-converting enzyme, N-[1(S)-carboxy-(4-OH-3-[125I]-phenyl) ethyl]-L-alanyl-L-proline (125I-CPAP), was injected as a bolus in the right heart of anesthetized ventilated rabbits and arterial blood was diverted through a flow-cell cuvette directly apposed to the phoswich detector. Single-pass extraction of 125I-CPAP was 39 +/- 3% (mean +/- SE; n = 20) and was depressed in a dose-dependent fashion by the addition of unlabeled CPAP (1-10 micrograms/kg) to the injection. These data indicate that we can now quantify, in the intact animal, saturable binding of an inhibitor to angiotensin-converting enzyme expressed on the surface of the pulmonary microvascular endothelium. Furthermore, such data can be obtained rapidly.

Animals↗

Use and prognostic value of staging mediastinoscopy in non-small-cell lung cancer.

One hundred sixty patients had preoperative mediastinoscopy, resection of the primary tumor, and complete mediastinal lymphadenectomy for non-small-cell carcinoma of the lung. Minimum follow-up was 24 months (mean 40 months). Postoperative staging based on histologic examination of the specimen of the lung and mediastinal lymphadenectomy categorized 59 patients in stage I, 28 in stage II, and 73 in stage III (20 T3N0, 12 T3N1, 29 T1 or T2N2, and 12 T3N2). The sensitivity rate of cervical mediastinoscopy for detection of mediastinal node metastasis was 48.7%. False-negative results of mediastinoscopy occurred in 21 of 41 patients with normal mediastinoscopy: unreachable nodes in eight patients, sampling error of reachable nodes in 11 patients, and error on frozen section in two patients. Eleven of 65 patients with clinical stage I disease and normal mediastinum on chest roentgenogram had mediastinal node involvement; only three were detected by mediastinoscopy, which resulted in a low sensitivity rate (27.3%) and a high rate of unnecessary mediastinoscopy (62/65 patients). The sensitivity of mediastinoscopy increased as the amount of disease present, as measured by the clinical stage of disease or positive gallium 67 scan of mediastinum, increased. Eleven of 29 patients with T1 to T2N2 disease discovered at mediastinoscopy had similar survival rates compared with 18 of 29 patients who had a normal mediastinoscopy examination and mediastinal node involvement discovered at thoracotomy.

Carcinoma, Non-Small-Cell Lung↗